由两种不同金属元素组成的双金属纳米材料(Bimetallic nanomaterials (BMNs) are one kind of innovative nanomaterials, referring to nano-bimetallic alloy, intermetallic compounds, or the combination of two kinds of metallic nanoparticles. Compared with monometallic nanomaterials, BMNs perform similar or even better physical and chemical properties in the medical field. BMNs possess excellent physical and chemical properties, such as easy surface modification, superior photothermal properties, multiple catalytic properties, delicate sensitivity, and good stability. Synthesis methods of bimetallic nanomaterials. The preparation methods of BMNs commonly used for cancer therapy, such as co-reduction method, hydrothermal method, seed-mediated growth method, and electrodeposition method.MNs)具有一定的混合模式和几何结构,它们通常比单金属纳米材料具有优越的性能。双金属基纳米材料因其独特的形貌和结构、特殊的理化性质、优异的生物相容性和协同效应,在生物医学领域得到了广泛的研究和广泛的应用,特别是在癌症治疗领域。
Generally, doping with the second metal is considered to possess superior performance than monometallic nanomaterials (MMNs), due to the addition of more active sites by the formation of metal polar bonds and irregular arrangement.[1][2] At the same time, the combination of the two metals is more likely to form complex structures with enhanced surface plasmon resonance (SPR) effects such as hollow structures, porous structures, and core-shell structures.[3] Therefore, regulating the optical, electrical, chemical, and biological properties by controlling their size, shape, and composition during synthesis is particularly important in the study of monometallic nanomaterials (BMNs).[4] In order to achieve the design and effects, many methods have been extensively tested in the past decades. Among them, there is an important problem that the ratio of the two metals and the shape of BMNs are difficult to control.[5] BMNs with controlled composition can be synthesized by co-reduction method and hydrothermal method, and their shapes are mostly spherical and massive. BMNs synthesized by seed-mediated method usually perform complex shapes, while the BMNs obtained by electrodeposition are mostly nanowires and nanofilms. In order to obtain suitable BMNs for cancer therapy, a systematic understanding of the synthesis methods is required.
一般来说,与第二种金属的掺杂被认为比MMNs具有优越的性能,因为通过形成金属极性键和不规则排列增加了更多的活性位点[16,17]。同时,两种金属的组合更有可能形成具有增强SPR效应的复杂结构,例如中空结构,多孔结构和核壳结构[18]。因此,在合成过程中通过控制其大小、形状和组成来调节光学、电学、化学和生物学特性在BMN的研究中尤为重要[19]。为了达到设计和效果,在过去的几十年中,许多方法都经过了广泛的测试。其中,存在一个重要问题,即两种金属的比例和BMN的形状难以控制[20]。可采用共还原法和水热法合成成分受控的BMNs,其形状多为球形和块状。通过种子介导的方法合成的BMN通常具有复杂的形状,而通过电沉积获得的BMN大多是纳米线和纳米薄膜。为了获得适合癌症治疗的BMN,需要对合成方法有系统的了解。Co-reduction is one of the most straightforward and convenient methods to prepare BMNs due to its simple operation, low cost, and short reaction time. Co-reduction, also known as the one-pot method, is usually used when two precursors containing metal elements are mixed, and the metal ions are reduced to form alloys or intermetallic compounds.[6][7] In addition, the BMNs’ morphology and structure can be tailored by the reaction temperature, the addition of surfactants, the reducing agent, and the nature of coordination ligand. Many common BMNs such as gold/silver core-shell structures, gold/silver nanowires, and gold/platinum nanoparticles (NPs) are synthesized by this method. More sophisticated nanomaterials with special shapes and structures can be synthesized by co-reduction in combination with other methods.[8]
具有特殊形状和结构的更复杂的纳米材料可以通过共还原与其他方法相结合来合成。Joo等人使用共还原和模板辅助合成制备了嵌入Au纳米颗粒(AgCM / AuNPs)的单分散银立方体到网状纳米结构[27]。AgCM/AuNPs由6个具有相似纳米结构的等效面板组成,由于基于网状纳米结构的大表面积,具有很高的等离子体光催化剂。Takeuchi等人提出了电偶置换反应与共还原剂的组合,以合成具有空心颗粒壳结构的金核(Au@Ag@Pt core@multishell)上Ag-Pt双壳的金属NPs[28]。Hydrothermal method is another widely used method, which is similar to the co-reduction method. The metal precursors are promoted to decompose and reduce after heating. The hydrothermal method is generally applicable to reactions with lower reduction potentials that are not easily reduced directly. Up to date, some BMNs synthesized from metal precursors with lower reduction potentials have been prepared with this method, such as CuNi,[9][10] Ni-Fe,[11] CoNi,[12] and NiRe.[13] Besides, the hydrothermal method is not only suitable for metal precursors with low reducibility but also widely used in the synthesis of many BMNs (PtCu, PtPd, et al., for instance).[14][15] In a word, the hydrothermal method is simple to operate and easy to synthesize large quantities of BMNs.
种子介导的生长已被证明是合成等离子体贵金属纳米晶体的有效方法[38]。该方法已应用于BMN的合成,因为制备的纳米晶体具有明确的形态,尺寸和表面组成。通常,种子介导的方法在制备各向异性金属结构和分层外延核/壳结构中起着重要作用[39,40,41,42]。Xia等人报道了在水溶液中合成Au@Ag核壳纳米立方体的简单途径[43]。首先,通过还原HAuCl合成非常小(2-3 nm)的Au纳米微晶4与纳布4在十六烷基三甲基溴化铵(CTAB)的溶液中。然后,HAuCl4、十六烷基三甲基氯化铵(CTAC)和L-抗坏血酸水溶液(AA)溶于超纯水中,然后加入3 nm Au NPs。混合物从无色变成红色,表明形成了更大的金种子。然后,将CTAC-Au种子和CTAC水溶液混合并在磁力搅拌下加热。最后,特定体积的AgNO水溶液3同时注入AA和CTAC的溶液和水溶液以形成Au@Ag纳米立方体。在这项工作中,可以精确调整银壳的厚度和Au@Ag的大小,该方法应该比其他方法更环保。 除了Au-Ag BMNs,这种方法也可以轻松合成其他一些具有高活性的新型金属BMN。Cargnello的小组开发了一种种子介导的方法来合成单分散Pt。x铜100-x具有受控Pt/Cu比率的纳米晶体合金[44]。他们证明了单个纳米晶体中的Pt和Cu以及Pt成功地合金化了x铜100-x具有受控的成分。种子介导生长法在合成BMNs领域因操作简单、重复性强、产量高而出现。特别是,BMN的形状和成分可以通过种子介导的方法精确调控,这是其他方法难以获得的。相信这种方法将来会得到更广泛的应用。Seed-mediated growth has been proven an effective method for synthesizing plasmonic noble metal nanocrystals.[16] This method has been applied in the synthesis of BMNs because the prepared nanocrystals have well-defined morphology, size, and surface composition. Typically, seed-mediated methods play an important role in the preparation of anisotropic metal structures and hierarchical epitaxial core/shell structures.[17][18][19][20] Seed-mediated growth method has emerged in the field of synthesizing BMNs due to simple operation, strong repeatability, and high yield. In particular, the shapes and components of BMNs can be accurately regulated by the seed-mediated method, which is difficult to obtain by other methods. It is believed that this method will be more extensively used in the future.
BMNs exhibit various and complex morphologies based on spatial arrangements, which are related to abundant physicochemical properties. Common nanomaterials used in disease treatment are mainly manifested as nanospheres, nanorods, nanoclusters, nanostars, and nanoflowers, which have large surface areas and unique optical properties. BMNs with specific morphology and structure can be obtained by different synthesis methods for the treatment of tumor.
In summary, many complex and diverse morphologies can be exhibited in BMNs that indicate the suitable characteristics for tumor therapy, such as good biocompatibility, drug-loading capacity, photothermal and catalytic properties. BMNs have a broad development prospect in tumor therapy by virtue of these abundant morphologies. BMNs have been widely used in biomedical fields, especially in biosensing and imaging, due to their unique catalytic and optical properties. In addition, many studies have shown that BMNs are also promising nanotechnology in cancer therapy.
However, it is still challenging to find suitable synthetic methods from many methods that can be used to produce BMNs for cancer therapy. It has been found that BMNs with zero dimension, such as spheres, rods, stars, and flowers, are usually used in cancer treatment. These structures are usually synthesized by seed-mediated and hydrothermal methods, where the regulation of BMNs' morphology has been well studied. In addition, it is also suggested that the growth pattern and mechanisms of all BMNs can be thoroughly explored by molecular simulation to establish a material library so that nanostructures with specific properties and shapes can be designed more clearly to reply to complex environments and various therapeutic applications.