School of Materials Science and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India.
Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India.
ACS Biomater Sci Eng. 2024 May 13;10(5):2636-2658. doi: 10.1021/acsbiomaterials.3c01749. Epub 2024 Apr 12.
Nanosized mesoporous silica has emerged as a promising flexible platform delivering siRNA for cancer treatment. This ordered mesoporous nanosized silica provides attractive features of well-defined and tunable porosity, structure, high payload, and multiple functionalizations for targeted delivery and increasing biocompatibility over other polymeric nanocarriers. Moreover, it also overcomes the lacunae associated with traditional administration of drugs. Chemically modified porous silica matrix efficiently entraps siRNA molecules and prevents their enzymatic degradation and premature release. This Review discusses the synthesis of silica using the sol-gel approach and the advantages with different silica mesostructure. Herein, the factors affecting the synthesis of silica at nanometer scale, shape, porosity and nanoparticle surface modification are also highlighted to attain the desired nanostructured silica carriers. Additional emphasis is given to chemically modified silica delivering siRNA, where the silica nanoparticle surface was modified with different chemical moieties such as amine modified with (3-aminoropyl) triethoxysilane, polyethylenimine, chitosan, poly(ethylene glycol), and cyclodextrin polymer modification to attain high therapeutic loading, improved dispersibility and biocompatibility. Upon systemic administration, ordered mesoporous nanosized silica encounters blood cells, immune cells, and organs mainly of the reticuloendothelial system (RES). Thereby, biocompatibility and biodistribution of silica based nanocarriers are deliberated to design principles for smart and efficacious nanostructured silica-siRNA carriers and their clinical trial status. This Review further reports the future scopes and challenges for developing silica nanomaterial as a promising siRNA delivery vehicle demanding FDA approval.
纳米介孔二氧化硅已成为一种很有前途的用于癌症治疗的 RNA 干扰递药的柔性平台。这种有序介孔纳米二氧化硅具有良好的定义和可调孔隙率、结构、高载药率和多种功能化等吸引人的特点，可用于靶向递药，并提高生物相容性，优于其他聚合物纳米载体。此外，它还克服了与传统药物给药相关的空白。化学修饰的多孔硅基质有效地将 siRNA 分子包埋在内，并防止其酶降解和过早释放。本文综述了溶胶-凝胶法合成二氧化硅及其不同二氧化硅介孔结构的优点。本文还强调了影响纳米级、形状、孔隙率和纳米颗粒表面修饰的二氧化硅合成的因素，以获得所需的纳米结构二氧化硅载体。此外，本文还重点介绍了通过化学修饰的二氧化硅递送 siRNA，其中通过不同的化学基团对二氧化硅纳米颗粒表面进行修饰，如用（3-氨丙基）三乙氧基硅烷修饰的胺、聚乙烯亚胺、壳聚糖、聚乙二醇和环糊精聚合物修饰，以获得高治疗载药量、改善分散性和生物相容性。在系统给药后，有序介孔纳米二氧化硅会遇到血细胞、免疫细胞和主要属于网状内皮系统（RES）的器官。因此，讨论了基于二氧化硅的纳米载体的生物相容性和生物分布，以设计智能和有效的纳米结构二氧化硅-siRNA 载体的设计原则及其临床试验状况。本文进一步报告了开发作为具有 FDA 批准前景的有前途的 siRNA 递送载体的纳米二氧化硅材料的未来范围和挑战。
