Two-Dimensional Nanomaterials for Biomedical Applications

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1		Ali Akbar Ashkarran	--	4113	2022-03-31 16:43:11	\|
2	corrected the format	Dean Liu	-22 word(s)	4091	2022-04-01 03:18:09	\|

This entry is adapted from the peer-reviewed paper 10.3390/jfb13010027

Two-dimensional nanomaterials (2DNMs) received remarkable attention in nanomedicine as a class of new nanomaterials in recent years. 2DNMs, which range from nanometer to micrometer scales, have one or a few atomic thicknesses and are one of the most promising materials for biomedical applications owing to their special structure and unique properties.

two-dimensional nanomaterials bioelectronics imaging drug delivery

1. Bioelectronics

Due to their specific geometry and unique physicochemical properties such as high conductivity and flexibility, 2D nanomaterials are appropriate choices for many bioelectronic applications (e.g., wearable sensors)^[1]^[2]^[3]^[4]. One of the earliest 2DNMs that has been widely investigated in the field of wearable electronics, is graphene nanosheets. In a recent study by Kwon and co-workers, high-aspect ratio functionalized conductive graphene are produced through exfoliation of graphite in ammonium sulfate solution. The obtained ink with defined concentration was used for printing gel-free wireless flexible electrodes for monitoring muscle activities. The all-printed stretchable electrode prepared through so-called “all printed nanomembrane hybrid electronics” technology (p-NHE), with superior compatibility to human skin was used for real-time electromyogram (EMG) recording. The electrode was attached on the three muscles with highest EMG signals: palmaris longus, brachioradialis, and flexor carpi ulnaris, which produced seven signal clusters by sensing motions of fingers. The NHE wearable electrode detects all finger motions for seven different gestures and accuracy as much as 99% through wireless monitoring of EMG signals via Bluetooth, denoting its ability for smart rehabilitation purposes ^[5].

Graphene can also be attached to biological interfaces with high conductivity (more than 2.6 S·m⁻¹) and conformity to make tissue-integrated biointerfaces ^[6]. In this method, graphene oxide- Polyvinyl alcohol (PVA) hydrogel is first reduced to become conductive reduced graphene oxide (rGO-PVA) before introducing poly (acrylic acid) grafted with N-hydroxysuccinimide (PAA-NHS) ester to make biointerface with wet tissue. The biofunctionality of electrodes in vivo was tested by implanting the electrode in the right atrium and apex of a rat heart, by which stable epicardial ECG with high signal to noise ratio was monitored. It was found that after 14 days the ECG signals became stronger, as a proof of successful biointerface integration ^[7]. Another noninvasive class of biointerfaces are temporary electronic tattoos for integration to human skin. These cheap accessible biointerfaces can be used to monitor human body status such as recording brain, heart and muscle activities. Kireev et al. developed a facile protocol to obtain graphene electronic tattoos using commercially available CVD-grown graphene without the need for trained labor. They found bilayer graphene electronic tattoos show skin impedance in the range of 8–10 kΩ and sheet resistance as low as 1 kΩ/sq compared to monolayer graphene, suggesting reproducible performance of bilayer graphene with low enough impedance to allow current injection ^[8].

Although applications of 2DNMs in bioelectronics were first fueled by the emergence of graphene, recently nongraphene 2D materials (e.g., MXenes) have been investigated extensively in biosensors and wearable technologies due to their functionality and physiochemical features that outperform other 2DNMs (i.e., graphene) for biomedical applications. 2D MXenes are conductive thin platforms with high surface area containing chemically reactive sites useful for biofunctionalization. These functional groups make the surface of MXenes hydrophilic compared to other similar 2DNMs, which allows solution preparation of MXenes in aqueous media. Moreover although high conductivity can also be obtained by other materials such as metal NPs and graphene, there are still drawbacks to their application in wearable biocompatible devices ^[9]. For instance, toxicity of metal NPs is debatable ^[9], and they normally need a high temperature annealing process which makes them inappropriate for room temperature polymer-based substrates ^[10]. Graphene, on the other hand, needs to be obtained by graphene oxide reduction ^[11], which needs high temperature thermal treatment in the presence of hazardous chemicals, ending up in a less hydrophilic layer not good enough for water-based ink solutions ^[12]. This is why MXenes, with high conductivity and hydrophilicity, are appropriate alternatives for flexible and implantable bioelectronic devices. MXenes have been utilized in facilitating charge transfer between electrode and redox enzymes in the enzymatic biosensor technologies due to their superior electrical conductivity. Therefore, they have been good substitutes for other conducting nanomaterials, thanks to their biocompatibility.

Black phosphorene (BP) is another class of 2DNMs which can be prepared by exfoliating black phosphorus crystal with high charge carrier mobility, which makes it suitable for electronic devices. However, exfoliated BP has intrinsic instability in ambient conditions, and is prone to degradation and oxidation in air and water environments ^[13]. One way to passivate BP against corrosion is to combine it with other conductive stable 2D materials such as MXene. In a study performed by Zhu and co-workers ^[14], titanium carbide MXene (Ti₃C₂-MXene) nanohybrid with two-dimensional phosphorene was prepared by electrostatic self-assembly. The nanomaterial then was mounted on laser-induced porous graphene and used as a nonenzymatic electrode for detection of phytoregulator α-naphthalene acetic acid (NAA) residues in agricultural products through a portable wireless electrochemical miniworkstation. The sensor revealed a wide linear range of 0.02–40 μM and a low limit of detection (LOD) of 1.6 nM ^[14]. Antimonene with similar properties to BP also holds much attention for biosensor application ^[15]. In a study, antimonene functionalized with supramolecular oligonucleotide and was applied to detect certain DNA sequences and BRCA1 gene mutation caused by breast cancer in real samples ^[16]. Therefore, this class of 2DNMs with the facile preparation method can potentially be an inexpensive alternative for traditional time-consuming gene assays.

Nanostructured topological insulators are narrow bandgap 2D materials with high carrier mobility, catalytic activity and delocalized metallic surface states that allow fast interfacial charge dynamic, which leads to highly sensitive electrochemical sensing platforms ^[17]. Zhao and co-workers synthesized microflakes of Bi₂Te₃ with a sensitivity of 4900 μAmM⁻¹cm⁻² and LOD of 10⁻⁸ molar for electroreduction of hydrogen peroxide, which was greatly enhanced compared to other available metal electrochemical sensors ^[18].

Cai and co-workers prepared sandwich-like Ti₃C₂T_x MXene/carbon nanotube (CNT) composite using a layer-by-layer air-spray coating of Ti₃C₂T_x and CNTs. The sensitivity of the device obtained from probing to piezoresistive properties of film through gauge factor relation GF = (R − R₀)/R₀ε (ε, R₀ and R are strain, electrical resistance with no strain, electrical resistance with strain, respectively) revealed a rapid increase at high strain due to disconnection between CNT routes. The sensor was used as a real-time monitoring wearable device to detect physiological movements. It was attached to a human throat while the volunteer was expressing various words with different syllables, and it was able to distinguish between them, indicating the potential application of this sensor for phonation rehabilitation exercises

2. Imaging

One fascinating and broad use of 2D nanomaterials is their implementation in the imaging technologies such as magnetic resonance imaging (MRI), X-Ray computed tomography imaging (CT imaging), optical imaging (OI) and PA imaging for diagnosing various diseases. It is reported that among various available 2DNMS, MOFs are promising materials for imaging applications due to their unique characteristics such as diverse compositions, high porosity, simplicity of their multifunctionalization and stability in physiological environments which enables their use as imaging contrast agents or imaging contrast carriers ^[19]^[20]. Recent research has revealed that through incorporation of Fe, Mn, Gd, iron oxide and derivatives into MOFs, specific types of nanocomposites can be generated that serve as contrast agents in MRIs and enhanced high-resolution MRIs. In addition, encapsulating superparamagnetic NPs into the MOFs makes them an appropriate nanocomposite as contrast agents ^[21]. Lin and co-workers decorated MOFs with Gd³⁺ for image contrast enhancement. Gd(BDC)_1.5(H₂O)₂, nanorods with 40 nm in diameter and 100 nm in length demonstrated the improvement of image contrast by increasing water proton relaxation rates for MRI imaging ^[22]. For CT imaging purposes, elements with high Z numbers such as barium, bismuth and iodine are used as contrast agents. However, many disadvantages such as large doses requirements in order to have satisfactory contrast and inadequate distribution have limited their practical applications ^[23]. In this regard, 2DNMs (e.g., MOF-based platforms) as next generation contrast agents can be introduced as an appropriate alternative to overcome these restrictions and contrast enhancement. For example, Shang and co-workers synthesized Au@MIL-88(A), the core-shell gold nanorod@MOF nanoprobes via tunable growth of a MOF shell layer on the surface of gold nanorod for multimodality diagnosis of glioma. This star-like nanocomposite with an average diameter of 89 ± 3 nm exhibited high contrast efficiency in CT imaging as well as in MRI and PAI imaging ^[24]. In addition to the abovementioned bio-imaging technologies, MOFs have shown high potential in the optical imaging field and there has been extensive research to fabricate MOFs with sufficient luminescence as bio-imaging agents. Lin and co-workers designed the phosphorescent MOF by [Ru{5,5′-(CO₂)₂-bpy}(bpy)₂] as a bridging ligand (bpy is 2,2′-bipyridine) and Zn²⁺ or Zr⁴⁺ as connecting points in which the zirconium MOF coated by silica and functionalized with PEG, targeted the cancer cells for in vitro optical imaging. Their findings show that the prepared nanocomposite is an efficient contrast optical imaging agent with extremely high dye loadings suitable for optical imaging ^[25].

Another fascinating 2D nanoplatform which has drawn considerable attention in biomedical applications is TMDs. Considering intriguing attributes such as relatively large surface-to-volume ratio allowing maximal interaction with target biomaterial and consequently enhanced efficiency and sensitivity, high stability in different environments, low toxicity, nonhazardous nature and desirable optical properties, TMDs are reported as a novel material for biomedical technologies ^[26]. Strong NIR absorbance, noticeable rate of light-to-heat transformation and the next generation of ultrasound signal meet requirements for application in PA imaging ^[27]. Chen and co-workers synthesized TMD-based nanosheets with different layers (single-layer (S-MoS₂), few-layer (F-MoS₂) and multi-layer (M-MoS₂)) using albumin-assisted exfoliation without further surface modifications with potential application in PA imaging ^[28]. It is reported that the number of layers in these MoS₂ nanosheets can significantly influence their PA effect. They reveal that reducing the number of layers in the nanosheets from M-MoS₂ to S-MoS₂ can result in outstanding enhancement in NIR absorbance, improvement in the elastic properties and excellent biocompatibility and production of a reinforced PA signal. These favorable features offer benefits of exploitation of single-layered MoS₂ in PA imaging probes. In vitro experiments of the prepared MoS₂ nanosheets indicate that intravenous injection of S-MoS₂ to U87 glioma cells of mice results in significantly efficient brain tumor cell detection. Moreover, the high atomic number and the excellent X-ray attenuation capability of transition metal in TMD nanostructures make them a desirable substitute in CT imaging techniques as contrast agents ^[29]. Yin and co-workers designed the chitosan functionalized MoS₂ (MoS₂-CS) nanosheets as a contrast agent of CT imaging. These chitosan modified MoS₂ nanosheets demonstrated prominent signal enhancement with an increase in the concentration of the agents in CT images of mice ^[30].

Another class of highly potential 2D nanomaterials in imaging technologies is topological insulators (TIs). Among different type of 2D TIs, Bi₂Se₃ nanosheets due to their high NIR absorption, bioactivity and biocompatibility have become more prominent in biomedical applications such as bioimaging. Xie and co-workers have proposed administration of two Bi₂Se₃ nanosheets with different sizes (30 and 80 nm) for optical diagnostic and photothermal therapy ^[31]. Their findings suggest that both Bi₂Se₃ nanosheets have favorable performance in all investigated features such as photoacoustic effect, optical absorption and NIR photothermal. Nevertheless, the smaller one (Bi₂Se₃ with 30 nm size) shows better performance which makes it a more suitable candidate for bioimaging techniques

The sandwiched thin films were able to detect human body deformations with high sensitivity of up to 772.6 in the range of 30% to 130% strain and demonstrated significant stability after more than 5000 cycles ^[32].

3. Drug Delivery

2DNMs have shown a great potential for drug delivery applications. Their layered structure, which enables high surface-area-to-mass ratio, adequate cell intake and routes of chemical functionalization, allows them serve as platforms of drug delivery in various therapies such as chemotherapy ^[33]^[34]. The planar topology of 2DNMs, along with their ultrathin structure, offer benefits of enhancing drug delivery performance due to their large surface area. In fact, by creating anchoring sites for antitumor and therapeutic drug molecules, this property can lead to increasing loading efficiencies of drug carriers. These desirable features attributed to 2D nanostructures employed as nanoplatforms in drug delivery are not limited to possessing high capacity of drug release; low toxicity and facile surface modification are other fascinating characteristics of these materials resulting in ever-increasing interest and efforts to develop them for drug delivery applications ^[2]^[35]^[36]^[37].

One of the 2D nanostructures being evaluated in drug delivery nanosystems is layered double hydroxides (LDHs) nanosheets. Indeed, considering the results of several recent studies, these nanosheets exhibit superb performance in cancer therapies as nanocarriers. Possessing some exceptional characteristics such as the capability to be absorbed by some certain cancer cells resulting in then reduction of the possibility of endosmal effects, desirable performance in pH-responsive drug release because of high interlayer anion exchange and charge density, facile adsorption for drug molecules with negative charges, anionic antibodies and biological molecules due to the positive charge on the surface of these nanosheets and statistically significant low toxicity make them a rising star in drug delivery applications ^[2]^[33]. For instance, recently Peng and his co-workers reported the fabrication of Gd-doped LDH nanosheets through a bottom-up process that exhibit a promising advance in drug delivery and cancer therapies by nanocarriers ^[38]. These LDH nanosheets as nanoplatforms demonstrated extraordinary efficiency in drug loading of DOX and ICG. Compared to other reported 2D drug nanocarriers, these MLDHs hold first place in their capacity to drug load content (LC) with the highest LC level (797.36%) at almost 100% of encapsulation efficiency (EE = 99.67%). Results revealed favorable behavior of DOX&ICG/MLDH composites in pH trigged and NIR responsive drug release as well as their excellent biocompatibility, which allows them to be considered as a strong candidate to improve the efficiency of drug delivery processes and then anticancer activity.

4. Tissue Engineering

Tissue engineering is an intellectual alternative to restore deprived functions of various body tissues. 2D-based materials have outperformed other materials due to their unique properties such as superior electrical and mechanical properties, biocompatibility and the capability for functionalization. To assign proper biocompatible material, it is vital to pinpoint desired features related to the specific tissue and find the best material that fulfills those expectations. The selected material that easily adopts and mimic the biological medium while maintaining its original function is then considered for that specific tissue construction ^[39].

Graphene, due to its electrical conductivity, hardness, biodegradability and flexibility is one of the most well-known 2D materials in tissue engineering and implants ^[40]. Biocompatibility, flexibility and antibacterial properties of graphene-based 2D materials can provide a scaffold for artificial neural tissue engineering for nerve regeneration ^[41], articular cartilage tissue engineering ^[42] and prevention of bacterial growth in dental tissues ^[43]. Moreover, based on its mechanical stability, it can be utilized in tissues that require stiffness such as bone-tissue engineering. It can be combined with hydrogels ^[44], fibers ^[45], polymers ^[46] and other scaffolds to reinforce their mechanical properties. Kolanthai and co-workers prepared alginate−chitosan−collagen-graphene oxide (SA–CS–Col–GO) composite scaffold by freeze-drying and ionically crosslinking with calcium ions. Compared to scaffolds in which the microporous structure is not refined with GO nanosheets, SA–CS–Col–GO demonstrated better mechanical property with increased modulus to 0.87 ± 0.05 MPa at 40% strain, due to the hydrogen bond of GO (–OH and –COOH functional groups) with the hydroxyl group of SA. The SA–CS–Col–GO showed improved mouse osteoblast cell growth with a higher number of live cells in comparison to other scaffolds, suggesting that the GO incorporated scaffold can boost the osteoblast cell proliferation and reveal better biocompatibility. Moreover, the SA–CS–Col–GO scaffold gained more stability in water compared to non-GO filled samples and the swelling ratio was significantly decreased in water (pH 7) and PBS (pH 7.4) due to increased crosslinking in the presence of GO ^[47]. Another study by Li and co-workers was conducted by preparing a three-dimensional GO foam/polydimethylsiloxane/zinc silicate (GF/PDMS/ZS) composite scaffold through dip coating and hydrothermal synthesis method, to make a macroporous platform for bone-tissue engineering ^[48]. The mechanical strength of the composite was enforced by incorporating PDMS to GF because the compressive modulus increased. Furthermore, the porosity of GF/PDMS/ZS composite measured 87.35% compared to GF/PDMS scaffold with 70.16%, an important factor in bone tissue engineering. In vitro studies using laser confocal images of cells cocultured with GF/PDMS/ZS scaffold after 7 days revealed more mouse bone marrow mesenchymal stem cells (mBMSCs) grew than on GF, GF/PDMS scaffolds and expression of alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX-2) gens as markers of osteogenic differentiation were enhanced. For in vivo analysis, rabbits’ bone defects were treated with the GF/PDMS/ZS and revealed comparable bone formation after 12 weeks of implantation with no inflammatory reaction ^[48]. Incorporation of a graphene-silver-polycationic peptide (GAP) nanocomposite into chitosan (Cs) in the form of sponge can also provide a scaffold for wound healing ^[49]. Graphene with high surface area strengthens the scaffold with maximum tensile strength of 58.33 ± 1.99 MPa with increasing nanocomposite concentration due to the π−π interaction of graphene with the chitosan structure and enhances the stability. Hemocompatibility of the scaffold was not more than 2.9% hemolysis. Silver NPs and polycationic peptide induce an antimicrobial scaffold against Escherichia coli and Staphylococcus aureus ^[50]. The hydrophilic structure of a sponge scaffold due to its graphene-polycationic peptide nanocomposite decreases the blood clotting time to 60 s. In vivo wound-healing efficacy of a nanobiocomposite scaffold was studied using a Wistar rat model. After 14 days, the Cs-GAP100 nanobiocomposite film-treated rat group showed faster and complete healing, with the wound closure of 97.12 ± 2.65% compared to the control group ^[49]. In another study by Sharifi and co-workers, to enhance gelatin glycidyl methacrylate hydrogel, graphene-coated microspherical cavities were introduced in the structure by reverse solvent interface trapping method to make microspherical cavities covered by exfoliated graphene. The biocompatibility of the hybrid was tested by live-dead assays that demonstrated viability of more than 90% after maximum 7 days of cell culture compared to cells grown on a tissue culture well plate (TCP) positive control ^[51].

2DNMs can also be utilized for wound healing with antibacterial properties. In a study by Huang and co-workers, an ultrasonication-assisted liquid exfoliation technique was adopted to generate highly stable black phosphorous (BP) nanosheets using silk fibroin (SF) as an exfoliating agent for wound dressing ^[52]. SF modified-BP (BP@SF) antibacterial activity was tested with E. coli (Gram-negative) and B. subtilis (Gram-positive) bacteria as representative models. The bacteria cocultured plate with BP@SF was irradiated with NIR light followed by plate counting. Both bacteria’s viability reduced compared to applying either BP@SF dressing or NIR laser irradiation. The viability assay with confocal fluorescence images of E. coli or B. subtilis cells was also performed, where most E. coli and B. subtilis cells were found dead after NIR irradiation. SEM images of bacteria revealed a distorted appearance after irradiation, confirming the PTT performance of the BP@SF dressing in killing bacteria. The in vivo PTT results demonstrate wound repair of mice tissue after 5 days and the residual bacteria of skin treated with the PTT agent was tested through measuring their optical density (OD₆₀₀), and it was found that the OD value of BP@SF alone was higher than that of control sample since BP@SF dressing on the wound might partially produce phosphate or phosphonate after degradation. Moreover, no abnormality was detected in mice organs when some parts were sliced for hematoxylin and eosin (H&E) histological analysis. Therefore, the BP@SF dressing using silk fibroin as an exfoliating and stabilizer agent was able to effectively prevent bacterial infection and improve wound repair ^[52].

To increase the NIR-light-to-heat conversion efficiency of 2D nanomaterials, Kang and co-workers loaded photosensitizer 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H,12H-porphine (THPP) at the surface of antimonene nanosheets (Sb NSs) followed by poly(ethylene glycol) (PEG) modification ^[53]. This modification allowed photothermal conversion efficiency of 44.6% of Sb–THPP–PEG NSs higher than most of the photothermal agents reported by others ^[54]^[55]. The Sb–THPP–PEG NSs display a Z-scheme heterojunction between Sb and THPP light absorbers due to their relevant band levels and improved charge carrier separation with generation of oxygen species ¹O₂ by THPP and ^●O₂ by Sb NSs. The composite displayed high photostability when tested for a 5 min cycle (on/off) with laser (808 nm) irradiation with the highest achievable temperature of 52 °C with composite concentration of 200 μg mL⁻¹. The composite material was then applied to in vitro and in vivo antitumor experiments. The biocompatibility of the composite in vitro was tested by evaluating the cytotoxicity of the composite with a cell viability examination after treatments with the composite through MTT assay standard cancer cell model of MCF-7, HeLa, 4T1, and NHDF cells. When laser triggered, more than 90% cells were killed by Sb–THPP–PEG NSs with 808 and 660 nm laser irradiations, while without applying laser, above 90% of cells remained untreated. To perform in vivo tumor treatment experiments, nanocomposites were injected in the tail vein of mice. They were irradiated under the 660 nm or/and 808 nm laser after 24 h, which resulted in raising the temperature detected by infrared imager, while no temperature rise was detected for THPP under irradiation, confirming more efficient light-to-heat conversion efficiency of the composite. The tumor growth in mice was suppressed and continued the downward trend after 10 days when the composite was applied and 660 nm plus 808 nm laser illuminated at mice with the minimal tumor size compared to either using 660 nm or 808 nm laser. For in vivo toxicity examination of Sb–THPP–PEG NSs, the mice’s serum was collected after 1, 7, and 14 days of injection, and the standard biochemistry assay, blood hematology data and H&E staining revealed no obvious inflammation and tissue ablation in the prime organs of the mice ^[53]. As such, antimonene nanosheets can improve light to heat conversion efficiency when applied with other photosensitive materials, while maintaining the biocompatibility and tumor degradation strength.

In the mentioned study by Pan and co-workers, Ti₃C₂ MXene was applied to kill bone tumor via photothermal therapy before bone-tissue engineering process ^[56]. Composite 3D-printing bioactive glass (BG) scaffolds were integrated with Ti3C2 NSs called TBGS to achieve higher photothermal conversion efficiency in vivo. When TBGSs were exposed to an 808 nm laser irradiation for 10 min at a power density of 1.0 W cm⁻², the equilibrium temperature increased from 55 to 65 °C within 10 min, while the temperature of BGS in the same condition did not remarkably increase. The high photothermal stability of the MXene-integrated composite was proven by five 3 min (on/off cycles) of laser irradiation with no obvious alteration of heating curves. Furthermore, after the Saos-2 cells (osteosarcoma cells) were incubated with TBGSs and irradiated by 808 nm laser, less than 40% of Saos-2 cells survived in the TBGS + laser group, revealing the ability of TBGS for efficiently killing cancer cells by photothermal ablation. In vivo photothermal tumor ablation study of TBGS was investigated using female BALB/c nude mice bearing Saos-2 bone tumor. Under NIR laser irradiation, the surface temperature of TBGSs-implanted tumors escalated to a temperature of 63 °C within 2 min, while BGSs-implanted tumors experienced a small increase to about 37 °C. Moreover, the treated TBGSs-implanted tumors permanently, while in other treated groups the tumor began to grow continuously again after treatment. This shows that composite scaffold use provides the advantage of efficient photothermal conversion of 2D Ti3C2 MXene along with bone regeneration of BG scaffolds ^[56].

MOF can also be utilized for loading chemotherapeutics in photothermal therapy due to their super encapsulating property. In a study by Zhang and co-workers, curcumin was loaded on the ferric ion sites of MIL-100, followed by preparing polydopamine-modified hyaluronic acid (HA-PDA)-coated MIL-100 to engineer stable MOF nanoparticles (MCH NPs) to promote photothermal conversional efficiency ^[53]. MCH NPs shows considerable absorbance at 808 nm compared to slight NIR absorbance of MIL-100. Therefore, MIL-100 revealed almost no temperature enhancement under 808 nm laser irradiation in 6 min, whereas after being loaded with curcumin, the MC NPs temperature reached as much as 38.9 °C, due to interaction among Fe³⁺ in MIL-100 structure and phenol groups in curcumin. The photothermal conversion efficiency of the MCH NPs was evaluated as 20.98% when PDA was applied. Since HA-PDA is detached at acidic pH, which increases drug release, it is expected that in the tumor environment, curcumin release is accelerated. The cytotoxicity of MCH NPs was evaluated in HeLa cells, CHO cells, A549 cells, and MRC-5 cells under 808 nm laser irradiation for 5 min. The cells exhibited much lower viability compared to nonirradiated cells, confirming the chemophotothermal combinational therapy capability of MCH NPs. For in vivo photothermal analysis, the MCH NPs were injected into xenograft HeLa tumor-bearing mice, where the MCH NPs accumulated at the tumor site and achieved photoacoustic imaging-guided chemo-photothermal combinational tumor therapy to accomplish tumor ablation compared to curcumin or MCH NPs tumor inhibition strength. Based on these findings, researchers can conclude that MOF hollow structure can be a host to accumulate chemotherapeutics and gradually release based on pH releasing mechanism in the tumor location ^[53].

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Subjects: Nanoscience & Nanotechnology

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Ali Akbar Ashkarran

Sahar Daemi

Ebrahim Mostafavi

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Entry Collection: Biopharmaceuticals Technology

Update Date: 01 Apr 2022

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