Copper-Based Nanomaterials in Tumor-Targeted Photothermal Therapy/Photodynamic Therapy: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Wendy Huang and Version 1 by Duo Yu.

纳米技术是一种新兴且有前途的治疗工具，由于具有吸光特性的纳米材料（Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs）的发展，可能会提高光疗（PT）在抗肿瘤治疗中的有效性。肿瘤靶向PTs，如光热疗法（PTT）和光动力疗法（PDT），将光能转化为热量并产生积聚在肿瘤部位的活性氧（ROS）。ROS水平的增加在致癌和疾病发展过程中诱导氧化应激（OS）。由于铜（Cu）是人体中重要的微量元素，具有局部表面等离子体共振（LSPR）特性，Cu基NMs可以表现出良好的近红外（NIR）吸收和优异的光热性能。与其他治疗方式相比，) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. Compared with other therapeutic modalities, PTT/PDT可以精确地靶向肿瘤位置以杀死肿瘤细胞。此外，多种治疗方式可以与PTT / PDT结合使用，以使用基于Cu的NM治疗肿瘤。 can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs.

  • nanomaterials (NMs)
  • photodynamic therapy (PDT)
  • photothermal therapy (PTT)
  • copper (Cu)
  • Cu-based NMs
  • reactive oxygen species (ROS)

1. 简介Introduction

癌症是一种复杂的疾病，其特征是各种遗传缺陷。恶性肿瘤发病率的增加及其转移倾向是人类健康的主要威胁，导致死亡率升高[1,2]。传统的肿瘤治疗方式（包括手术、放疗和化疗）可引起各种不良反应，包括放射性损伤、化疗药物的毒副作用或化疗引起的多药耐药，这大大限制了这些方式的治疗效果[3Cancer is a complicated disease characterized by various genetic flaws. The increased incidence of malignant tumors and their predisposition for metastasis are major threats to human health, which lead to higher mortality rates [1][2]. The traditional treatment modalities for tumors, including surgery, radiotherapy, and chemotherapy, can engender various adverse effects, including radioactive damage, toxic side effects of chemotherapeutic drugs, or chemotherapy-induced multidrug resistance, which considerably limits the therapeutic effectiveness of these modalities [3][4][5][6]. The emerging treatment modalities for tumors, such as thermotherapy, immunotherapy, and gene therapy,4 have provided greater hope for patients [7][8]. However,5 their prolonged use has been reported to severely impair the immune system,6] even leading to organ malfunction [9][10]. Discovering a tumor treatment modality with low toxicity to healthy tissues and improved precision presents an imperative and formidable challenge.新兴的肿瘤治疗方式，如温热疗法、免疫疗法和基因疗法，为患者带来了更大的希望[7,8]。然而，据报道，长期使用它们会严重损害免疫系统，甚至导致器官功能障碍[9,10]。发现一种对健康组织毒性低且精度更高的肿瘤治疗方式是一项势在必行且艰巨的挑战。
最近，光疗（Recently, phototherapies (PTs），如光热疗法（PTT）和光动力疗法（PDT），被广泛用作有效的抗肿瘤治疗策略[10]。在), such as photothermal therapy (PTT) and photodynamic therapy (PDT), are being widely used as effective antitumor therapeutic strategies [10]. In PTT和 and PDT中，光热剂（PA）和光敏剂（PSs）在受肿瘤影响的器官中充当外源性能量转换器或吸收剂[11]。这使得可见光或激光能转化为热能，在高温下诱导肿瘤细胞凋亡或坏死，同时产生或不同时产生活性氧[12,13,14,15]。, photothermal agents (PAs) and photosensitizers (PSs) work as exogenous energy converters or absorbers in the organ affected by the tumor [11]. This has enabled the conversion of visible or laser light energy into thermal energy to induce apoptosis or necrosis of tumor cells at high temperatures, with or without concurrent reactive oxygen species (ROS) generation [12][13][14][15]. PT与其他基于热的肿瘤治疗技术（包括温热疗法和微波疗法）相比具有特定的优势。其高精度使 has specific advantages over other heat-based tumor treatment techniques, including thermotherapy and microwave therapy. Its high precision enables PT能够以尽可能小的损伤靶向肿瘤[16]。此外， to target tumors with the least possible damage to adjacent tissues and organs [16]. Additionally, PT是治疗肿瘤的绝佳方法，因为它具有可控性和低毒性特征。与单独作用的 is an excellent method for managing tumors because of its controllability and low toxicity profile. Compared with either PTT或PDT相比，PTT和PDT联合的协同方法可以加速肿瘤细胞死亡并提高治疗效果[17]。 or PDT acting alone, the synergistic approach combining PTT and PDT can hasten tumor cell death and increase the therapeutic efficacy [17]. The key components of PTT和 and PDT的关键成分是它们的PA和PS，目前主要包括纳米材料（NMs），它们与传统的大分子不同。NM表现出优异的特性，包括高布鲁诺尔-埃米特-泰勒（BET）、导电性、光吸收后的光谱偏移、荧光特性和降解潜力[18]。因此，它们已被稳步纳入癌症研究，推进了肿瘤研究领域[19 are their PAs and PSs, majorly including nanomaterials (NMs) at present, which differ from conventional macromolecules. NMs exhibit excellent characteristics, including high Brunauer–Emmett–Teller (BET), electrical conductivity, spectrum shifts after light absorption, fluorescence properties, and potential for degradation [18]. Therefore, they have been steadily incorporated into cancer research,20 advancing the field of tumor investigations [19][20][21]. Regarding medical therapeutics,2 materials of nanoscale dimensions (1]。关于医学治疗，已经采用了纳米级尺寸（直径1-100nm）的材料[22]。这些–100 nm diameter) have been employed [22]. These NM在药物运输中具有广泛的应用，可实现控释机制，增加渗透性，穿越生物屏障，并提高整体生物相容性[23,24,25]。由于其独特的大小和性状，s have versatile applications in drug transportation, enabling controlled release mechanisms, increasing permeability, traversing biological barriers, and improving overall biocompatibility [23][24][25]. Owing to their unique size and traits, NMs可以显着改变各种治疗过程，并显着提高治疗效果[22]。金属离子基 can remarkably change various therapeutic processes and considerably improve treatment efficacy [22]. Metal ion-based NM，包括金（s, including those of gold (Au）、银（Ag）、铜（Cu）和其他NM，表现出独特的光学特性，特别是局部表面等离子体共振（LSPR）现象[26,27]。), silver (Ag), copper (Cu), and other NMs, exhibit distinctive optical properties, notably the phenomenon of localized surface plasmon resonance (LSPR) [26][27]. LSPR基于金属离子基 notably strengthens the electric field in the immediate proximity of metal ion-based NM强烈吸收光子能量的能力，显着增强了它们附近的电场。由于广泛的光诱导效应和产生的分子间相互作用，它们被用于肿瘤靶向s, based on their capacity to strongly absorb photon energy. Owing to an extensive range of light-induced effects and intermolecular interactions produced, they are used in tumor-targeted PTT/PDT。然而，基于Au或Ag的NM的高成本以及一些PA/PS在体内的不可降解性限制了其在临床治疗中的应用[28]。. However, the high cost of Au- or Ag-based NMs and the non-degradability of some PAs/PSs in vivo limits their application in clinical therapy [28]. Cu是一种容易获得的金属，具有独特的生物活性，可用于通过调节各种类型的细胞死亡来消除肿瘤细胞[29]。此外，, a readily available metal, has unique bioactivities that can be used for eliminating tumor cells by regulating various types of cell death [29]. Furthermore, Cu可以进行类似芬顿的反应，以催化过量的细胞内过氧化氢（ can undergo a Fenton-like reaction to catalyze high ROS content from excess intracellular hydrogen peroxide (H2O2），可诱导细菌和肿瘤细胞死亡[30]。铜的功能和治疗参与如图), which can induce bacterial and tumor cell death [30]. The functions and therapeutic involvement of Cu are shown in Figure 1所示。. Al Kayal等人创造了覆盖有Cu纳米颗粒（NPs）的静电纺丝聚氨酯膜，并对大肠杆菌进行了抗菌测试，发现超过一半的细菌被破坏，显示出其强大的杀菌作用。此外， et al. created electrospun polyurethane membranes covered with Cu nanoparticles (NPs) and ran an antimicrobial test on Escherichia coli and discovered that over half of the bacteria were destroyed, showing its potent bactericidal effects. Additionally, SARS-CoVer-2抗病毒活性近 was resistant to the antiviral activity by nearly 90%[31]。近年来， [31]. Cu基-based NM因其具有强大的近红外（NIR）吸收和光热能力[32,33]、高s have been widely employed in PTT and PDT in recent years because of their advantageous properties, including strong near-infrared (NIR) absorption and photothermal capabilities [32][33], high BET[34,35]以及用于肿瘤成像等优势而广泛用于PTT和PDT。[36]此外，基于 [34][35], and use in tumor imaging. [36] Furthermore, Cu的-based NMs在肿瘤治疗中具有相当大的优势，因为它们的合成程序简单，并且在温和的低反应条件下具有相对较高的产量[37]。赵等人用铜合成了 offer considerable advantages in tumor therapy owing to their simple synthesis procedures and relatively high production yields under mild low reaction conditions [37]. Zhao et al. synthesized CCeT NMs（ (Ce：: Chlorin e6，T：, T: TPP-COOH）) with Cu2−x以硫（ Sulfur (S）为核心，在激光照射下光热转换效率（PCE）为10.6%。在非常低的浓度下，温度在5分钟内升高了3.10°C，并随着浓度的增加而继续升高[38]，证明了) as the core, which exhibited a photothermal conversion efficiency (PCE) of 10.6% under laser irradiation. At very low concentrations, the temperature increased by 5.3 °C in 10 min and continued to rise with increasing concentration [38], demonstrating the therapeutic advantages of PTT/PDT的治疗优势，并且使用 and that it can be substantially increased using Cu基NMs可以显着提高温度。-based NMs.
Pharmaceutics 15 02293 g001
图Figure 1.铜的功能和治疗参与。CDT：化学动力学治疗。
Functions of Cu and therapeutic involvement. CDT: chemodynamic therapy.

2. 氧化铜在Application of Copper Oxides in PTT和 and PDT中的应用

在过去的几十年中，各种基于 Over the past few decades, various Cu的-based NM已成为放大s have emerged as alternative means to amplify the effects of PTT/PDT效应的替代手段[119]。研究表明， [39]. Studies indicate that CuO-NPs可以阻碍胰腺肿瘤的生长，特别是通过靶向肿瘤干细胞[120]。这些 can hinder pancreatic tumor growth, notably by targeting tumor stem cells [40]. These NPs可以诱发线粒体功能障碍，归因于 can induce mitochondrial dysfunction, attributed to the ability of Cu2+通过芬顿样反应生成 to generate ROS，并通过C-2p和Cu-3d之间的电子跃迁增强PCE[121]。 through the Fenton-like reaction and to enhance PCE through electronic transitions between C-2p and Cu-3d [41]. Ma et a等人开发了l. developed CuO@CNSs-DOX（DOX：多柔比星）纳米平台，将PCE从6.7%提高到 (DOX: Doxorubicin) nanoplatforms, elevating the PCE from 6.7% to 10.14%。这些平台通过DOX的药物作用和产生·羟基自由基由铜. These platforms achieve anti-tumor effects through the drug action of DOX and the generation of ·OH radicals by Cu2+ [42][43]. [122,123]。同一组合成多功能The same group synthesized multifunctional MoS2-CuO@BSA/R837（ (MCBR，BSA：牛血清白蛋白，R837：咪喹莫特，一种toll样受体7（TLR7）激动剂）纳米花。在, BSA: Bovine Serum Albumin, R837: Imiquimod, a toll-like receptor 7 (TLR7) agonist) nanoflowers. Under 808 nm激光照射下， 这些纳米花的PCE为24.6%， ·哦生产。此外，R837的加入增加了CRT的表达，触发了ICD，有效地中和了原发性肿瘤，并抑制了转移性肿瘤[124]。利用铜的优势 laser exposure, these nanoflowers exhibited a PCE of 24.6% and a marked increase in ·OH production. Additionally, the inclusion of R837 increased the expression of calreticulin (CRT), triggering immunogenic cell death (ICD), effectively neutralizing primary tumors, and inhibiting metastatic tumors [44]. Taking advantage of Cu2O的折射率在’s high refractive index above 600nm以上，Yu等人制得的核/壳结构 nm, Yu et al. produced core/shell structured Cu@Cu2O@polymer NP。在s. Under a 660 nm 激光照射和等效铜浓度下，与laser exposure and an equivalent Cu concentration, compared to Cu@polymer NP 相比，温度升高s, the temperature increase for Cu@Cu2NPs O@polymer约为 NPs was about 4.2 °C。 这导致相邻组织中的温度升高至少. This resulted in a temperature rise of at least 23 °C，转化为 IC 中的 7 倍浪涌 in adjacent tissues, translating to a 7-fold surge in the IC50，相对于先前的研究[125,126]。这些发现强调了, relative to prior research [45][46]. These findings underscore that Cu@Cu2O@polymer NPs具有足够的光毒性来消灭肿瘤细胞。此外，内源性 possess sufficient phototoxicity to exterminate tumor cells. Furthermore, the increased concentration of endogenous H2O2 produced by the LPS内毒素产生的加速Cu离子和ROS的释放，促进癌细胞的根除[33,125]。
endotoxin accelerated the release of Cu ions and ROS, facilitating the eradication of cancer cells [33][45].

3. 铜的应用Application of CuxSy在 in PTT 和and PDT 中

半导体纳米管铜 Semiconductor NMs CuxSy由于其光学和电学特性，在催化和传感领域获得了吸引力。由于其经济实惠、细胞毒性最小和高光稳定性， have gained attraction in catalysis and sensing sectors due to their optical and electrical properties. Owing to their affordability, minimal cytotoxicity, and high photostability, CuxSy NP有希望作为PAs hold promise as Pas [47][48]. Tian et al. synthes[127,128]。田等合成了亲水、板状ized hydrophilic, plate-like Cu9S5纳米晶体。使用 nanocrystals. With a 980 nm激光器，铜的 laser, the PCE of Cu9S5达到 reached 25.7%。有趣的是，在相同条件下，该PCE超过了合成的Au纳米晶体，约为23.7%。这些纳米晶体在体内迅速（不到10分钟）根除肿瘤细胞，建立. Interestingly, under identical conditions, this PCE surpassed that of the synthesized Au nanocrystals, which was approximately 23.7%. These nanocrystals eradicated tumor cells in vivo swiftly (in less than 10 min), establishing Cu9S5纳米晶体作为高效的 nanocrystals as efficient PA。当激素小鼠在注射后接受后续辐射时，观察到肿块区肿瘤细胞明显坏死和萎缩[129,130]。针对非靶向超小金属s. When hormonal mice underwent subsequent radiation following injection, notable necrosis and shrinkage of tumor cells in the mass region were observed [49][50]. Addressing the challenge that non-targeted ultrasmall metallic NPs作为 face in securing prolonged half-life and satisfactory tumor-site aggregation as PTT试剂在确保延长半衰期和令人满意的肿瘤部位聚集方面面临的挑战，Li等人合成了 agents, Li et al. synthesized CuS NPs，并用西妥昔单抗（Ab）对其进行修饰以产生 and modified them with cetuximab (Ab) to yield CuS-Ab NPs。在暴露于1064nm激光10分钟时，温度从23°C迅速升高至58°C，并始终保持在58°C。 此外，Ab修饰使. On exposure to a 1064 nm laser for 10 min, temperatures increase rapidly from 23 °C to 58 °C and are consistently held at 58 °C. Additionally, Ab modification rendered CuS-Ab NPs在肿瘤靶向和抗血管生成能力方面具有优越性，可确保有效的肿瘤部位积累，而不会同时损害其他组织和器官[131]。 superior in tumor-targeting and anti-angiogenic capacities, ensuring effective tumor-site accumulation without concomitant damage to other tissues and organs [51]. Cationic polymers, such as PEI等阳离子聚合物可以通过加强阳离子在细胞膜上的静电吸附来实现药物递送[132]。研究表明，用, can achieve drug delivery by intensifying the electrostatic adsorption of cations on the cell membrane [52]. Studies have shown that NMs modified with PEI和 and PS修饰的NM有助于膀胱肿瘤的PDT[133]。基于此，s can be instrumental in the PDT of bladder tumors [53]. Based on this, Mu等人制备了 et al. prepared HRP@CPC@HA NPs（HRP：辣根过氧化物酶，CPC： (HRP: horseradish peroxidase, CPC: CuS-PEI-Ce6，HA：透明质酸）。这些颗粒将HRP掺入空心CuS纳米笼内[134]。在, HA: hyaluronic acid). These particles incorporated HRP within a hollow CuS nanocage [54]. Subjected to 808 nm激光辐射下，其PCE约为 laser radiation, their PCE was around 34.91%。同时，表面结合的Ce6被激活，导致大量的. Concurrently, the surface-bound Ce6 was activated, leading to a large amount of 1O2 generation, the levels of which increased alongside temperature [133][53]. Additionally, HRP catalyzed the breakdown of intracellular H2O2 to oxygen, addressing the oxygen deficit in tumor cells and facilitating simultaneous multimodal tumor eradication in severely hypoxic TME [135][55]. Due to the increased concentration of endogenous H2S in tumor cells, Wu et al. synthesize monolocking NPs (MLNPs) [136][56]. When illuminated with 808 nm radiation, these MLNPs combined with H2S and produced ultra-small CuS nanodots. This interaction elevated tumor temperatures, triggering apoptosis in tumor cells. Mel is released from the NPs which causes the COX-2 enzyme to become inactive, amplifying the PTT action and inhibiting inflammation induced by PTT damage. Notably, these NPs were excreted renally [137][57]. The development of nanomedicine has witnessed diverse manifestations of CuxSy. Hollow structured CuxSy has particularly piqued interest in oncologic therapy, attributed to its drug-loading ability and high PCE and PAI capability [138[58][59],139], yet many extant synthesis methods for CuS-based NMs are intricate, time-consuming, and require special reaction equipment. Consequently, there is an evident need for facile, cost-effective methodologies that employ gentle reaction conditions to fabricate CuxSy NMs.

4. Application of Copper Selenides and Copper Telluride in PTT and PDT

Copper selenides, notably Cu2-XSe NMs, present promising applications in imaging and PTT for cancer treatment, attributed to their biocompatibility, excellent NIR light absorption, and increased PCE [140,141][60][61].
Du et al. synthesized CuSe/NC-DOX-DNA NPs (NC: nitrogen-doped carbon) via an environmentally friendly and simple method. Under 808 nm laser exposure, these NPs displayed a PCE of 32.9%, surpassing that of Au nanorods which had a PCE of 22.0% [142][62]. Moreover, the synergistic action of photocatalysis combined with the Fenton-like reaction of CuSe/NC markedly augmented ROS generation [143][63]. Concurrently, the encapsulated DOX functioned as a chemotherapeutic agent, realizing a threefold enhanced PTT/CDT/PCT tumor treatment method [144][64]. It is noteworthy that Cu2-XSe has been identified as an effective PA [141][61]. In another study, He et al. developed ICG@Cu2-X Se-ZIF-8 (ICG: Indocyanine Green, ZIF-8: a metal-organic framework). After 808 nm laser exposure, this compound exhibited a PCE of 15.5%. In the TME, ZIF-8 breaks down and releases Cu1+ and Cu2+, which leads to a Fenton-like reaction, controls the amount of GSH, and produces ROS [145][65]. Furthermore, selenium has the ability to regulate selenoprotein, allowing it to prevent the production of osteoclasts and tumor cells, resulting in the synergistic PTT/CDT prevention of malignant bone metastasis [146,147][66][67]. Moreover, CuSe is an ideal PS and has been demonstrated to biodegrade. Selenium is released during this process and has been shown to lower the risk of liver cancer, lung cancer, and prostate cancer [148,149][68][69]. Pun et al. fabricated COF-CuSe NMs (COF: covalent-organic framework); under 808 nm laser irradiation, the PCE was 26.34% after injection in mice. A large quantity of 1O2 was generated under both 650 nm and 808 nm illumination. Consequently, almost all of the HeLa cells died under laser irradiation. The PTT and PDT anti-tumor treatment strategies showed a synergistic potential [150][70]. At present, CuSe NMs have been poorly investigated for PTT/PDT and the development of multifunctional CuSe NM is still required to improve anti-tumor therapy for PTT/PDT.
Similar to CuSe, CuTe is considered a novel PAs candidate. Li et al. created CuTe NPs with a plasma peak at 900 nm. Under 830 nm laser irradiation, the mortality of 3T3 embryonic fibroblasts increased [151][71]. However, it was discovered that some cells were already dead before laser irradiation. It has been demonstrated that CuTe NPs are cytotoxic and PAs. Under 1064 nm laser irradiation, bio Cu2−XTe nanosheets synthesized by Li et al. had a PCE of 48.6%. When Cu1+ and Te are released, the nanosheets can produce ·OH and inhibit the GPx and TrxR enzymes for CDT, significantly inhibiting the proliferation of MCF-7 cells [152][72]. Shen et al. synthesized CM CTNPs@OVA NMs (CM: melanoma B16-OVA membrane, OVA: ovalbumin) with solid CuTe NPs. Under laser irradiation, there was a significant increase in temperature and production of ROS. In addition, B16-OVA cells produced an abundance of ATP and HMGB-1, which effectively stimulated the immune system and enhanced the anti-tumor treatment [153][73]. CuTe NPs anti-tumor therapy research in PTT/PDT has received less attention and requires further development and investigation.

5. Application of Cu-Based Nanocomposites in PTT and PDT

Most treatments consisting of a single therapy have a negligible impact on tumor treatment. However, a synergistic combination of multiple therapeutic modalities can improve the efficacy of treating malignant tumors [154][74]. The same applies to NMs. In cancer treatment, simple Cu-based NMs such as CuS may still be lacking. Therefore, it is necessary to load various materials, drugs, or fluorescents onto Cu-based NMs to create a composite material capable of fluorescence, tumor targeting, and therapy in a single NM.
As a result of the discovery of cuproptosis, Cu-based NMs may induce tumor cell death by modulating the concentration of Cu in tumor cells, offering a novel anti-tumor therapeutic modality [111][75]. Pan et al. produced GOx@[Cu(tz)] NPs. Under 808 nm laser irradiation, NPs entering tumor cells produced H2O2 and ·OH. In the meantime, under the influence of GSH, GOx hydrolyzed and consumed glucose, generating a large amount of H2O2 and OH that produced a ROS-adding effect [155][76]. Due to the depletion of glucose and GSH, the NPs bind to lipoylated mitochondrial enzymes, resulting in the aggregation of lipoylated DLAT, which induces cuproptosis and effectively inhibits tumor growth (92.4% inhibition rate) [156][77]. The synthesis and development of NMs that combine multiple antitumor therapeutic modalities is urgently needed. Xia et al. synthesized metal-organic skeleton nanosheets Cu-TCPP(Al)-Pt-FA (TCPP: Tetrakis (4-carboxyphenyl) porphyrin, FA: folic acid) with surface modification by platinum NPs (Pt NPs) and FA in order to solve the problem of poor oxygenation in tumor tissues. Compared to 25.2% tumor cell survival in vitro without laser irradiation, laser irradiation at 638 nm reduced tumor cell survival to 20.7%. Since Cu2+ can react with GSH via a Fenton-like reaction, it depletes intracellular GSH and increases ROS levels [157][78]. In the meantime, Pt NPs have catalysis activity comparable to a catalase-like reaction that can continuously convert intracellular H2O2 to O2 in order to alleviate hypoxic TME and enhance the therapeutic effect of PDT [158][79]. ROS concentration was increased synergistically by these two modalities, which stimulated antigen-presenting cells to activate systemic anti-tumor immune responses and increased the infiltration of cytotoxic T lymphocytes (CTLs) at the tumor site for synergistic immune anti-tumor therapy [159,160][80][81]. Xu et al. constructed d-Cu-LDH/ICG NPs (LDH: lactatedehydrogenase) in order to alleviate the tumor hypoxia problem and avoid the poor therapeutic effect caused by tumor hypoxia during PDT treatment [161][82]. Under 808 nm laser irradiation, the PCE was 88.7% and the production of 1O2 increased as the temperature rose. In the meantime, the rising temperature led to the dissolution of the NMs and the reduction in Cu2+ to Cu1+ by GSH, both of which can consume excessive H2O2 and generate OH in tumor cells via a Fenton-like reaction, resulting in CDT and modulation of the TME [162][83]. In the meantime, it was demonstrated that hormonal mice had significantly less tumor growth. Hematoxylin and eosin (H&E) staining of major organs revealed no obvious inflammation or damage and demonstrated that the effective anti-tumor agent exhibited no significant systemic toxicity. Yang et al. created NSCuCy NPs containing Cu1+ as the core [163][84]. Cu1+ undergoes a Fenton-like reaction with O2− to produce ·OH [164][85]. The fluorescence intensity of the HPF was used to detect the ROS concentration; it was discovered that the fluorescence intensity of the HPF increased rapidly in the presence of NSCuCy NPs under 660 nm irradiation. At pH 5.5, the emission intensity of HPF increased nearly 350-fold after 10 min of irradiation, demonstrating a higher ·OH production efficiency than that at pH 7.4 (180-fold) and targeting accumulation in tumor tissues to achieve complete tumor ablation [165][86]. Kang et al. developed Au@MSN-Cu/PEG/DSF NPs (Au@MSN: mesoporous silica-coated Au nanorods, DSF: disulfiram). The PCE under 808 nm laser irradiation is 56.32%. With an increase in temperature, the Cu-doped SiO2 framework begins to biodegrade. During the conversion of Cu2+ to Cu1+, releasing DSF can chelate with Cu2+ to produce highly cytotoxic bis (diethyldithiocarbamate) Cu (CuET) [166,167][87][88]. Cu1+ binds additionally to mitochondrial protein aggregates during the TCA cycle, inducing cuproptosis in tumor cells [111][75]. Photothermal therapy′s synergistic effect resulted in an 80.1% tumor inhibition rate, effectively killing tumor cells and inhibiting tumor growth [111,168][75][89].
Overall, multifunctional nanocomposite materials that integrate imaging, diagnosis, and therapy have shown significant improvements in tumor treatment compared to single-material therapy. These NMs combine PTT/PDT with drug delivery systems, immunotherapy, and chemotherapy, reducing normal medication dosage and adverse reactions while achieving effective anti-tumor treatment in the short term. However, long-term experimental data on NMs are still needed to verify their long-term toxicity, biosafety, and therapeutic effects to ensure they meet desired goals. Further investigations are required for a comprehensive understanding.

6. Application of Cu-MOF in PTT and PDT

Metal-organic frameworks (MOFs) are a novel type of NMs that combine metal ions or clusters with multisite organic ligands. These MOFs have shown great potential in anti-tumor therapy due to their inherent biodegradability, high porosity, structural diversity, and high drug-loading capacity [170,171,172,173][90][91][92][93].
For instance, Wu et al. synthesized ultrathin Cu-TCPP MOF nanosheets containing both Cu1+ and Cu2+ which enabled imaging, photothermal conversion, and anti-tumor therapy [36,174][36][94]. Under 808 nm laser irradiation, the nanosheets showed a PCE of 36.8% and a significant amount of 1O2 was generated in tumor cells. Cu2+ has unpaired 3d electrons and paramagnetic also allowed the nanosheets to be used for T1-weighted MRI. This multifunctional NMOF design holds promise for tumor PTT [59][95]. Tang et al. designed two metal-organic materials, MOF-1 and MOF-2, based on this premise. MOF-1 is an aluminum (AL)-MOF that does not contain Cu2+, whereas MOF-2 is an AL-Cu mixed-metal MOF[CuL-[AlOH]2n with Cu2+ at its core. Comparing the two MOFs under 650 nm laser irradiation revealed that MOF-2 has a porous physical structure, which makes the Cu2++ in MOF-2 significantly adsorb intracellular GSH and results in a decrease in GSH and an increase in ROS concentration, which enhances the efficacy of PDT [175][96]. Similar to the chemotherapeutic drug camptothecin (CPT), MOF-2 was able to eradicate tumor cells in an in vivo experiment. The results of a simultaneous examination of major organ tissue slices revealed little toxicity in vivo [176,177][97][98]. This MOF structure, which simultaneously decreases intracellular GSH levels and increases intracellular ROS levels, may provide not only a new strategy for intracellular GSH adsorption but also a new method for enhancing PDT.
Due to the higher cavity structure of emerging Cu-NMOFs, they can be loaded with more PSs or PAs to improve PCE and increase the diffusion range of ROS. Their porous structure also allows for chemotherapeutic drug delivery and synergistic effects with other therapies to enhance anti-tumor efficacy. However, the synthesis process of MOF PSs or PAs can be complex and might exhibit batch-to-batch variations, hindering large-scale NMOF preparation. Moreover, the presence of various metal ions necessitates further investigation into the long-term safety, biocompatibility, pharmacokinetics, and immunoreactivity of NMOFs in mammals through systematic animal studies.

References

  1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249.
  2. Song, G.; Chen, Y.; Liang, C.; Yi, X.; Liu, J.; Sun, X.; Shen, S.; Yang, K.; Liu, Z. Catalase-Loaded TaOx Nanoshells as Bio-Nanoreactors Combining High-Z Element and Enzyme Delivery for Enhancing Radiotherapy. Adv. Mater. 2016, 28, 7143–7148.
  3. Cabrita, R.; Lauss, M.; Sanna, A.; Donia, M.; Skaarup Larsen, M.; Mitra, S.; Johansson, I.; Phung, B.; Harbst, K.; Vallon-Christersson, J.; et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature 2020, 577, 561–565.
  4. Arroyo-Hernández, M.; Maldonado, F.; Lozano-Ruiz, F.; Muñoz-Montaño, W.; Nuñez-Baez, M.; Arrieta, O. Radiation-induced lung injury: Current evidence. BMC Pulm. Med. 2021, 21, 9.
  5. Holohan, C.; Van Schaeybroeck, S.; Longley, D.B.; Johnston, P.G. Cancer drug resistance: An evolving paradigm. Nat. Rev. Cancer 2013, 13, 714–726.
  6. Chari, R.V.; Miller, M.L.; Widdison, W.C. Antibody-drug conjugates: An emerging concept in cancer therapy. Angew. Chem. Int. Ed. Engl. 2014, 53, 3796–3827.
  7. Seynhaeve, A.L.B.; Amin, M.; Haemmerich, D.; van Rhoon, G.C.; Ten Hagen, T.L.M. Hyperthermia and smart drug delivery systems for solid tumor therapy. Adv. Drug. Deliv. Rev. 2020, 163, 125–144.
  8. Gulzar, A.; Wang, Z.; He, F.; Yang, D.; Zhang, F.; Gai, S.; Yang, P. An 808 nm Light-Sensitized Upconversion Nanoplatform for Multimodal Imaging and Efficient Cancer Therapy. Inorg. Chem. 2020, 59, 4909–4923.
  9. Zhang, L.X.; Sun, X.M.; Xu, Z.P.; Liu, R.T. Development of Multifunctional Clay-Based Nanomedicine for Elimination of Primary Invasive Breast Cancer and Prevention of Its Lung Metastasis and Distant Inoculation. ACS Appl. Mater. Interfaces 2019, 11, 35566–35576.
  10. Hou, Y.J.; Yang, X.X.; Liu, R.Q.; Zhao, D.; Guo, C.X.; Zhu, A.C.; Wen, M.N.; Liu, Z.; Qu, G.F.; Meng, H.X. Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles. Int. J. Nanomed. 2020, 15, 6827–6838.
  11. Li, Y.; Wen, T.; Zhao, R.; Liu, X.; Ji, T.; Wang, H.; Shi, X.; Shi, J.; Wei, J.; Zhao, Y.; et al. Localized Electric Field of Plasmonic Nanoplatform Enhanced Photodynam ic Tumor Therapy. ACS Nano 2014, 8, 11529–11542.
  12. Zhang, Y.; Yang, D.; Chen, H.; Lim, W.Q.; Phua, F.S.Z.; An, G.; Yang, P.; Zhao, Y. Reduction-sensitive fluorescence enhanced polymeric prodrug nanoparticles for combinational photothermal-chemotherapy. Biomaterials 2018, 163, 14–24.
  13. Melamed, J.R.; Edelstein, R.S.; Day, E.S. Elucidating the fundamental mechanisms of cell death triggered by photothermal therapy. ACS Nano 2015, 9, 6–11.
  14. Sobis, H.; Waer, M.; Vandeputte, M. Normal and malignant trophoblasts do not recruit granulated metrial gland cells. Tumour Biol. 1996, 17, 13–19.
  15. Liu, Y.; Bhattarai, P.; Dai, Z.; Chen, X. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem. Soc. Rev. 2019, 48, 2053–2108.
  16. Cai, X.; Gao, W.; Zhang, L.; Ma, M.; Liu, T.; Du, W.; Zheng, Y.; Chen, H.; Shi, J. Enabling Prussian Blue with Tunable Localized Surface Plasmon Resonanc es: Simultaneously Enhanced Dual-Mode Imaging and Tumor Photothermal T herapy. ACS Nano 2016, 10, 11115–11126.
  17. Jin, T.; Cheng, D.; Jiang, G.; Xing, W.; Liu, P.; Wang, B.; Zhu, W.; Sun, H.; Sun, Z.; Xu, Y.; et al. Engineering naphthalimide-cyanine integrated near-infrared dye into ROS-responsive nanohybrids for tumor PDT/PTT/chemotherapy. Bioact. Mater. 2022, 14, 42–51.
  18. Zanganeh, N.; Guda, V.K.; Toghiani, H.; Keith, J.M. Sinter-Resistant and Highly Active Sub-5 nm Bimetallic Au–Cu Nanoparticle Catalysts Encapsulated in Silica for High-Temperature Carbon Monoxide Oxidation. ACS Appl. Mater. Interfaces 2018, 10, 4776–4785.
  19. Cheng, Z.; Li, M.; Dey, R.; Chen, Y. Nanomaterials for cancer therapy: Current progress and perspectives. J. Hematol. Oncol. 2021, 14, 85.
  20. Giodini, L.; Re, F.L.; Campagnol, D.; Marangon, E.; Posocco, B.; Dreussi, E.; Toffoli, G. Nanocarriers in cancer clinical practice: A pharmacokinetic issue. Nanomedicine 2017, 13, 583–599.
  21. Yun, Y.H.; Lee, B.K.; Park, K. Controlled Drug Delivery: Historical perspective for the next generation. J. Control. Release 2015, 219, 2–7.
  22. Ali, E.S.; Sharker, S.M.; Islam, M.T.; Khan, I.N.; Shaw, S.; Rahman, M.A.; Uddin, S.J.; Shill, M.C.; Rehman, S.; Das, N.; et al. Targeting cancer cells with nanotherapeutics and nanodiagnostics: Current status and future perspectives. Semin. Cancer Biol. 2021, 69, 52–68.
  23. Osaki, T.; Yokoe, I.; Sunden, Y.; Ota, U.; Ichikawa, T.; Imazato, H.; Ishii, T.; Takahashi, K.; Ishizuka, M.; Tanaka, T.; et al. Efficacy of 5-Aminolevulinic Acid in Photodynamic Detection and Photodynamic Therapy in Veterinary Medicine. Cancers 2019, 11, 495.
  24. Gao, W.; Wang, Z.; Lv, L.; Yin, D.; Chen, D.; Han, Z.; Ma, Y.; Zhang, M.; Yang, M.; Gu, Y. Photodynamic Therapy Induced Enhancement of Tumor Vasculature Permeability Using an Upconversion Nanoconstruct for Improved Intratumoral Nanoparticle Delivery in Deep Tissues. Theranostics 2016, 6, 1131–1144.
  25. Xu, M.; Zhou, L.; Zheng, L.; Zhou, Q.; Liu, K.; Mao, Y.; Song, S. Sonodynamic therapy-derived multimodal synergistic cancer therapy. Cancer Lett. 2021, 497, 229–242.
  26. Lee, H.E.; Ahn, H.Y.; Mun, J.; Lee, Y.Y.; Kim, M.; Cho, N.H.; Chang, K.; Kim, W.S.; Rho, J.; Nam, K.T. Amino-acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles. Nature 2018, 556, 360–365.
  27. Jian, C.-C.; Zhang, J.; Ma, X. Cu–Ag alloy for engineering properties and applications based on the LSPR of metal nanoparticles. RSC Adv. 2020, 10, 13277–13285.
  28. Gezgin, S.Y.; Kepceoğlu, A.; Gündoğdu, Y.; Zongo, S.; Zawadzka, A.; Kiliç, H.; Sahraoui, B. Effect of Ar Gas Pressure on LSPR Property of Au Nanoparticles: Comparison of Experimental and Theoretical Studies. Nanomaterials 2020, 10, 1071.
  29. Xue, Q.; Kang, R.; Klionsky, D.J.; Tang, D.; Liu, J.; Chen, X. Copper metabolism in cell death and autophagy. Autophagy 2023, 19, 2175–2195.
  30. Lin, B.; Chen, H.; Liang, D.; Lin, W.; Qi, X.; Liu, H.; Deng, X. Acidic pH and High-H2O2 Dual Tumor Microenvironment-Responsive Nanocatalytic Graphene Oxide for Cancer Selective Therapy and Recognition. ACS Appl. Mater. Interfaces 2019, 11, 11157–11166.
  31. Al Kayal, T.; Giuntoli, G.; Cavallo, A.; Pisani, A.; Mazzetti, P.; Fonnesu, R.; Rosellini, A.; Pistello, M.; D’Acunto, M.; Soldani, G.; et al. Incorporation of Copper Nanoparticles on Electrospun Polyurethane Memb rane Fibers by a Spray Method. Molecules 2023, 28, 5981.
  32. Zhang, W.X.; Hao, Y.N.; Gao, Y.R.; Shu, Y.; Wang, J.H. Mutual Benefit between Cu(II) and Polydopamine for Improving Photothermal-Chemodynamic Therapy. ACS Appl. Mater. Interfaces 2021, 13, 38127–38137.
  33. Tai, Y.W.; Chiu, Y.C.; Wu, P.T.; Yu, J.; Chin, Y.C.; Wu, S.P.; Chuang, Y.C.; Hsieh, H.C.; Lai, P.S.; Yu, H.P.; et al. Degradable NIR-PTT Nanoagents with a Potential Cu@Cu2O@Polymer Structure. ACS Appl. Mater. Interfaces 2018, 10, 5161–5174.
  34. Yuan, H.; Xia, P.; Sun, X.; Ma, J.; Xu, X.; Fu, C.; Zhou, H.; Guan, Y.; Li, Z.; Zhao, S.; et al. Photothermal Nanozymatic Nanoparticles Induce Ferroptosis and Apoptosis through Tumor Microenvironment Manipulation for Cancer Therapy. Small 2022, 18, e2202161.
  35. Xu, N.; Hu, A.; Pu, X.; Wang, J.; Liao, X.; Huang, Z.; Yin, G. Cu-Chelated polydopamine nanoparticles as a photothermal medium and “immunogenic cell death” inducer for combined tumor therapy. J. Mater. Chem. B 2022, 10, 3104–3118.
  36. Zhou, M.; Tian, M.; Li, C. Copper-Based Nanomaterials for Cancer Imaging and Therapy. Bioconjug. Chem. 2016, 27, 1188–1199.
  37. Aishajiang, R.; Liu, Z.; Wang, T.; Zhou, L.; Yu, D. Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy. Molecules 2023, 28, 2303.
  38. Xiang, H.; Xue, F.; Yi, T.; Tham, H.P.; Liu, J.-G.; Zhao, Y. Cu2-xS Nanocrystals Cross-Linked with Chlorin e6-Functiona lized Polyethylenimine for Synergistic Photodynamic and Photothermal T herapy of Cancer. ACS Appl. Mater. Interfaces 2018, 10, 16344–16351.
  39. Zhong, X.; Dai, X.; Wang, Y.; Wang, H.; Qian, H.; Wang, X. Copper-based nanomaterials for cancer theranostics. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2022, 14, e1797.
  40. Benguigui, M.; Weitz, I.S.; Timaner, M.; Kan, T.; Shechter, D.; Perlman, O.; Sivan, S.; Raviv, Z.; Azhari, H.; Shaked, Y. Copper oxide nanoparticles inhibit pancreatic tumor growth primarily b y targeting tumor initiating cells. Sci. Rep. 2019, 9, 12613.
  41. Liu, Y.; Zhen, W.; Jin, L.; Zhang, S.; Sun, G.; Zhang, T.; Xu, X.; Song, S.; Wang, Y.; Liu, J.; et al. All-in-One Theranostic Nanoagent with Enhanced Reactive Oxygen Species Generation and Modulating Tumor Microenvironment Ability for Effective Tumor Eradication. ACS Nano 2018, 12, 4886–4893.
  42. Rehman, S.U.; Zubair, H.; Sarwar, T.; Husain, M.A.; Ishqi, H.M.; Nehar, S.; Tabish, M. Redox cycling of Cu(II) by 6-mercaptopurine leads to ROS generation and DNA breakage: Possible mechanism of anticancer activity. Tumour Biol. 2015, 36, 1237–1244.
  43. Jiang, F.; Ding, B.; Zhao, Y.; Liang, S.; Cheng, Z.; Xing, B.; Teng, B.; Ma, P.A.; Lin, J. Biocompatible CuO-decorated carbon nanoplatforms for multiplexed imaging and enhanced antitumor efficacy via combined photothermal therapy/chemodynamic therapy/chemotherapy. Sci. China Mater. 2020, 63, 1818–1830.
  44. Jiang, F.; Ding, B.; Liang, S.; Zhao, Y.; Cheng, Z.; Xing, B.; Ma, P.A.; Lin, J. Intelligent MoS2–CuO heterostructures with multiplexed imaging and remarkably enhanced antitumor efficacy via synergetic photothermal therapy/chemodynamic therapy/ immunotherapy. Biomaterials 2021, 268, 120545.
  45. Palashuddin Sk, M.; Goswami, U.; Ghosh, S.S.; Chattopadhyay, A. Cu2+-embedded carbon nanoparticles as anticancer agents. J. Mater. Chem. B 2015, 3, 5673–5677.
  46. Yuan, R.; Xu, H.; Liu, X.; Tian, Y.; Li, C.; Chen, X.; Su, S.; Perelshtein, I.; Gedanken, A.; Lin, X. Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Human Cancer Cells through Reactive Oxygen Species-Mediated NF-κB Activations. ACS Appl. Mater. Interfaces 2016, 8, 31806–31812.
  47. Han, L.; Zhang, Y.; Chen, X.W.; Shu, Y.; Wang, J.H. Protein-modified hollow copper sulfide nanoparticles carrying indocyanine green for photothermal and photodynamic therapy. J. Mater. Chem. B 2016, 4, 105–112.
  48. Chen, G.; Ma, B.; Wang, Y.; Xie, R.; Li, C.; Dou, K.; Gong, S. CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging. ACS Appl. Mater. Interfaces 2017, 9, 41700–41711.
  49. Tian, Q.; Jiang, F.; Zou, R.; Liu, Q.; Chen, Z.; Zhu, M.; Yang, S.; Wang, J.; Wang, J.; Hu, J. Hydrophilic Cu9S5 nanocrystals: A photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo. ACS Nano 2011, 5, 9761–9771.
  50. Tian, Q.; Tang, M.; Sun, Y.; Zou, R.; Chen, Z.; Zhu, M.; Yang, S.; Wang, J.; Wang, J.; Hu, J. Hydrophilic flower-like CuS superstructures as an efficient 980 nm laser-driven photothermal agent for ablation of cancer cells. Adv. Mater. 2011, 23, 3542–3547.
  51. Li, B.; Jiang, Z.; Xie, D.; Wang, Y.; Lao, X. Cetuximab-modified CuS nanoparticles integrating near-infrared-II-responsive photothermal therapy and anti-vessel treatment. Int. J. Nanomed. 2018, 13, 7289–7302.
  52. Kolawole, O.M.; Lau, W.M.; Khutoryanskiy, V.V. Methacrylated chitosan as a polymer with enhanced mucoadhesive properties for transmucosal drug delivery. Int. J. Pharm. 2018, 550, 123–129.
  53. Li, G.; Yuan, S.; Deng, D.; Ou, T.; Li, Y.; Sun, R.; Lei, Q.; Wang, X.; Shen, W.; Cheng, Y.; et al. Fluorinated Polyethylenimine to Enable Transmucosal Delivery of Photosensitizer-Conjugated Catalase for Photodynamic Therapy of Orthotopic Bladder Tumors Postintravesical Instillation. Adv. Funct. Mater. 2019, 29, 1901932.
  54. Mu, X.; Chang, Y.; Bao, Y.; Cui, A.; Zhong, X.; Cooper, G.B.; Guo, A.; Shan, G. Core-satellite nanoreactors based on cationic photosensitizer modified hollow CuS nanocage for ROS diffusion enhanced phototherapy of hypoxic tumor. Biomater. Adv. 2023, 145, 213263.
  55. Feng, L.; Zhao, R.; Liu, B.; He, F.; Gai, S.; Chen, Y.; Yang, P. Near-Infrared Upconversion Mesoporous Tin Oxide Bio-Photocatalyst for H2O2Activatable O2-Generating Magnet ic Targeting Synergetic Treatment. ACS Appl. Mater. Interfaces 2020, 12, 41047–41061.
  56. Akbari, M.; Sogutdelen, E.; Juriasingani, S.; Sener, A. Hydrogen Sulfide: Emerging Role in Bladder, Kidney, and Prostate Malignancies. Oxid. Med. Cell. Longev. 2019, 2019, 2360945.
  57. Feng, L.; Wu, S.; Wu, Y. Intracellular Bottom-up Synthesis of Ultrasmall CuS Nanodots in Cancer Cells for Simultaneous Photothermal Therapy and COX-2 Inactivation. Adv. Funct. Mater. 2021, 31, 2101297.
  58. Shi, H.; Sun, Y.; Yan, R.; Liu, S.; Zhu, L.; Liu, S.; Feng, Y.; Wang, P.; He, J.; Zhou, Z.; et al. Magnetic Semiconductor Gd-Doping CuS Nanoparticles as Activatable Nanoprobes for Bimodal Imaging and Targeted Photothermal Therapy of Gastric Tumors. Nano Lett. 2019, 19, 937–947.
  59. Zhao, R.; Sun, X.; Sun, J.; Wang, L.; Han, J. Polypyrrole-modified CuS nanoprisms for efficient near-infrared photothermal therapy. RSC Adv. 2017, 7, 10143–10149.
  60. Liu, X.; Law, W.-C.; Jeon, M.; Wang, X.; Liu, M.; Kim, C.; Prasad, P.N.; Swihart, M.T. Cu2-x Se nanocrystals with localized surface plasmon resonance as sens itive contrast agents for in vivo photoacoustic imaging: Demonstration of sentinel lymph node mapping. Adv. Healthc. Mater. 2013, 2, 952–957.
  61. Zhang, S.; Sun, C.; Zeng, J.; Sun, Q.; Wang, G.; Wang, Y.; Wu, Y.; Dou, S.; Gao, M.; Li, Z. Ambient Aqueous Synthesis of Ultrasmall PEGylated Cu2xSe Nanoparticles as a Multifunctional Theranostic Agent for Multimodal Imaging Guided Photothermal Therapy of Cancer. Adv. Mater. 2016, 28, 8927–8936.
  62. Zeng, J.; Goldfeld, D.; Xia, Y. A plasmon-assisted optofluidic (PAOF) system for measuring the phototh ermal conversion efficiencies of gold nanostructures and controlling a n electrical switch. Angew. Chem. 2013, 52, 4169–4173.
  63. Wang, Y.; Li, Z.; Hu, Y.; Liu, J.; Guo, M.; Wei, H.; Zheng, S.; Jiang, T.; Sun, X.; Ma, Z.; et al. Photothermal conversion-coordinated Fenton-like and photocatalytic rea ctions of Cu2-xSe-Au Janus nanoparticles for tri-combinatio n antitumor therapy. Biomaterials 2020, 255, 120167.
  64. Yan, H.; Dong, J.; Luan, X.; Wang, C.; Song, Z.; Chen, Q.; Ma, J.; Du, X. Ultrathin Porous Nitrogen-Doped Carbon-Coated CuSe Heterostructures fo r Combination Cancer Therapy of Photothermal Therapy, Photocatalytic T herapy, and Logic-Gated Chemotherapy. ACS Appl. Mater. Interfaces 2022, 14, 56237–56252.
  65. Gao, L.; Chen, Q.; Gong, T.; Liu, J.; Li, C. Recent advancement of imidazolate framework (ZIF-8) based nanoformulat ions for synergistic tumor therapy. Nanoscale 2019, 11, 21030–21045.
  66. Liu, T.; Xu, L.; He, L.; Zhao, J.; Zhang, Z.; Chen, Q.; Chen, T. Selenium nanoparticles regulates selenoprotein to boost cytokine-induc ed killer cells-based cancer immunotherapy. Nano Today 2020, 35, 100975.
  67. Zou, B.; Xiong, Z.; He, L.; Chen, T. Reversing breast cancer bone metastasis by metal organic framework-cap ped nanotherapeutics via suppressing osteoclastogenesis. Biomaterials 2022, 285, 121549.
  68. Hessel, C.M.; Pattani, V.P.; Rasch, M.; Panthani, M.G.; Koo, B.; Tunnell, J.W.; Korgel, B.A. Copper selenide nanocrystals for photothermal therapy. Nano Lett. 2011, 11, 2560–2566.
  69. Kumar, P.; Singh, K.; Srivastava, O.N. Template free-solvothermaly synthesized copper selenide (CuSe, Cu2−xSe, β-Cu2Se and Cu2Se) hexagonal nanoplates from different precursors at low temperature. J. Cryst. Growth 2010, 312, 2804–2813.
  70. Hu, C.; Zhang, Z.; Liu, S.; Liu, X.; Pang, M. Monodispersed CuSe Sensitized Covalent Organic Framework Photosensitizer with an Enhanced Photodynamic and Photothermal Effect for Cancer Therapy. ACS Appl. Mater. Interfaces 2019, 11, 23072–23082.
  71. Li, W.; Zamani, R.; Rivera Gil, P.; Pelaz, B.; Ibáñez, M.; Cadavid, D.; Shavel, A.; Alvarez-Puebla, R.A.; Parak, W.J.; Arbiol, J.; et al. CuTe Nanocrystals: Shape and Size Control, Plasmonic Properties, and U se as SERS Probes and Photothermal Agents. J. Am. Chem. Soc. 2013, 135, 7098–7101.
  72. Zhou, G.; Li, M. Biodegradable copper telluride nanosheets for redox-homeostasis breaki ng-assisted chemodynamic cancer therapy boosted by mild-photothermal e ffect. Chem. Eng. J. 2022, 450, 138348.
  73. Fang, T.; Ma, S.; Wei, Y.; Yang, J.; Zhang, J.; Shen, Q. Catalytic immunotherapy-photothermal therapy combination for melanoma by ferroptosis-activating vaccine based on artificial nanoenzyme. Mater. Today Chem. 2023, 27, 101308.
  74. Zhang, Q.; Li, L. Photodynamic combinational therapy in cancer treatment. J. Buon. 2018, 23, 561–567.
  75. Tsvetkov, P.; Coy, S.; Petrova, B.; Dreishpoon, M.; Verma, A.; Abdusamad, M.; Rossen, J.; Joesch-Cohen, L.; Humeidi, R.; Spangler, R.D.; et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science 2022, 375, 1254–1261.
  76. Fu, L.H.; Qi, C.; Lin, J.; Huang, P. Catalytic chemistry of glucose oxidase in cancer diagnosis and treatment. Chem. Soc. Rev. 2018, 47, 6454–6472.
  77. Xu, Y.; Liu, S.Y.; Zeng, L.; Ma, H.; Zhang, Y.; Yang, H.; Liu, Y.; Fang, S.; Zhao, J.; Xu, Y.; et al. An Enzyme-Engineered Nonporous Copper(I) Coordination Polymer Nanoplatform for Cuproptosis-Based Synergistic Cancer Therapy. Adv. Mater. 2022, 34, e2204733.
  78. Zhang, H.; Liu, K.; Li, S.; Xin, X.; Yuan, S.; Ma, G.; Yan, X. Self-Assembled Minimalist Multifunctional Theranostic Nanoplatform for Magnetic Resonance Imaging-Guided Tumor Photodynamic Therapy. ACS Nano 2018, 12, 8266–8276.
  79. Wang, X.-S.; Zeng, J.-Y.; Zhang, M.-K.; Zeng, X.; Zhang, X.-Z. A Versatile Pt-Based Core-Shell Nanoplatform as a Nanofactory for Enha nced Tumor Therapy. Adv. Funct. Mater. 2018, 28, 1801783.
  80. Chen, Z.; Wu, Y.; Yao, Z.; Su, J.; Wang, Z.; Xia, H.; Liu, S. 2D Copper(II) Metalated Metal-Organic Framework Nanocomplexes for Dual-enhanced Photodynamic Therapy and Amplified Antitumor Immunity. ACS Appl. Mater. Interfaces 2022, 14, 44199–44210.
  81. Huang, Z.; Chen, Y.; Zhang, J.; Li, W.; Shi, M.; Qiao, M.; Zhao, X.; Hu, H.; Chen, D. Laser/GSH-Activatable Oxaliplatin/Phthalocyanine-Based Coordination Polymer Nanoparticles Combining Chemophotodynamic Therapy to Improve Cancer Immunotherapy. ACS Appl. Mater. Interfaces 2021, 13, 39934–39948.
  82. Yan, L.; Gonca, S.; Zhu, G.; Zhang, W.; Chen, X. Layered double hydroxide nanostructures and nanocomposites for biomedical applications. J. Mater. Chem. B 2019, 7, 5583–5601.
  83. Sun, L.; Wang, J.; Liu, J.; Li, L.; Xu, Z.P. Creating Structural Defects of Drug-Free Copper-Containing Layered Double Hydroxide Nanoparticles to Synergize Photothermal/Photodynamic/Chemodynamic Cancer Therapy. Small Struct. 2021, 2, 2000112.
  84. Zhang, J.; Mukamel, S.; Jiang, J. Aggregation-Induced Intersystem Crossing: Rational Design for Phosphorescence Manipulation. J. Phys. Chem. B 2020, 124, 2238–2244.
  85. Chen, H.; Tian, J.; He, W.; Guo, Z. H2O2-Activatable and O2-Evolving Nanoparticles for Highly Efficient and Selective Photodynamic Therapy against Hypoxic Tumor Cells. J. Am. Chem. Soc. 2015, 137, 1539–1547.
  86. Yang, J.; Wang, Y.; Qin, G.; Tian, T.; Ran, J.; Wang, H.; Yang, C. Photogeneration of Hydroxyl Radicals Based on Aggregation-Induced Emission Luminogen-Assembled Copper Cysteamine Nanoparticles for Photodynamic Therapy. ACS Appl. Nano Mater. 2023, 6, 533–543.
  87. Skrott, Z.; Majera, D.; Gursky, J.; Buchtova, T.; Hajduch, M.; Mistrik, M.; Bartek, J. Disulfiram’s anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase. Oncogene 2019, 38, 6711–6722.
  88. Wu, W.; Yu, L.; Jiang, Q.; Huo, M.; Lin, H.; Wang, L.; Chen, Y.; Shi, J. Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition. J. Am. Chem. Soc. 2019, 141, 11531–11539.
  89. Zhou, J.; Yu, Q.; Song, J.; Li, S.; Li, X.L.; Kang, B.K.; Chen, H.Y.; Xu, J.J. Photothermally Triggered Copper Payload Release for Cuproptosis-Promoted Cancer Synergistic Therapy. Angew. Chem. Int. Ed. Engl. 2023, 62, e202213922.
  90. Peng, Y.; Li, Y.; Ban, Y.; Jin, H.; Jiao, W.; Liu, X.; Yang, W. Membranes. Metal-organic framework nanosheets as building blocks for molecular sieving membranes. Science 2014, 346, 1356–1359.
  91. Wang, D.; Zhou, J.; Shi, R.; Wu, H.; Chen, R.; Duan, B.; Xia, G.; Xu, P.; Wang, H.; Zhou, S.; et al. Biodegradable Core-shell Dual-Metal-Organic-Frameworks Nanotheranostic Agent for Multiple Imaging Guided Combination Cancer Therapy. Theranostics 2017, 7, 4605–4617.
  92. Wang, S.; Shang, L.; Li, L.; Yu, Y.; Chi, C.; Wang, K.; Zhang, J.; Shi, R.; Shen, H.; Waterhouse, G.I.; et al. Metal-Organic-Framework-Derived Mesoporous Carbon Nanospheres Containing Porphyrin-Like Metal Centers for Conformal Phototherapy. Adv. Mater. 2016, 28, 8379–8387.
  93. Park, J.; Jiang, Q.; Feng, D.; Mao, L.; Zhou, H.C. Size-Controlled Synthesis of Porphyrinic Metal-Organic Framework and Functionalization for Targeted Photodynamic Therapy. J. Am. Chem. Soc. 2016, 138, 3518–3525.
  94. Li, B.; Ye, K.; Zhang, Y.; Qin, J.; Zou, R.; Xu, K.; Huang, X.; Xiao, Z.; Zhang, W.; Lu, X.; et al. Photothermal theragnosis synergistic therapy based on bimetal sulphide nanocrystals rather than nanocomposites. Adv. Mater. 2015, 27, 1339–1345.
  95. Li, B.; Wang, X.; Chen, L.; Zhou, Y.; Dang, W.; Chang, J.; Wu, C. Ultrathin Cu-TCPP MOF nanosheets: A new theragnostic nanoplatform with magnetic resonance/near-infrared thermal imaging for synergistic phototherapy of cancers. Theranostics 2018, 8, 4086–4096.
  96. Ju, E.; Dong, K.; Chen, Z.; Liu, Z.; Liu, C.; Huang, Y.; Wang, Z.; Pu, F.; Ren, J.; Qu, X. Copper(II)-Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation and Reduced Glutathione Levels for Enhanced Photodynamic Therapy. Angew. Chem. Int. Ed. Engl. 2016, 55, 11467–11471.
  97. Zhang, W.; Lu, J.; Gao, X.; Li, P.; Zhang, W.; Ma, Y.; Wang, H.; Tang, B. Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with Cu(II) as the Active Center. Angew. Chem. Int. Ed. Engl. 2018, 57, 4891–4896.
  98. Fateeva, A.; Chater, P.A.; Ireland, C.P.; Tahir, A.A.; Khimyak, Y.Z.; Wiper, P.V.; Darwent, J.R.; Rosseinsky, M.J. A water-stable porphyrin-based metal-organic framework active for visible-light photocatalysis. Angew. Chem. Int. Ed. Engl. 2012, 51, 7440–7444.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Video Production Service
Feedback