Department of Pharmaceutical Sciences, CPBN, Northeastern University, Boston, Massachusetts; Department of Chemistry, Shah Jalal University of Science and Technology, Sylhet, Bangladesh.
Department of Pharmaceutical Sciences, CPBN, Northeastern University, Boston, Massachusetts.
Transl Res. 2019 Dec;214:62-91. doi: 10.1016/j.trsl.2019.07.006. Epub 2019 Jul 22.
Nanocarriers as drug delivery systems are promising and becoming popular, especially for cancer treatment. In addition to improving the pharmacokinetics of poorly soluble hydrophobic drugs by solubilizing them in a hydrophobic core, nanocarriers allow cancer-specific combination drug deliveries by inherent passive targeting phenomena and adoption of active targeting strategies. Nanoparticle-drug formulations can enhance the safety, pharmacokinetic profiles, and bioavailability of locally or systemically administered drugs, leading to improved therapeutic efficacy. Gene silencing by RNA interference (RNAi) is rapidly developing as a personalized field of cancer treatment. Small interfering RNAs (siRNAs) can be used to switch off specific cancer genes, in effect, "silence the gene, silence the cancer." siRNA can be used to silence specific genes that produce harmful or abnormal proteins. The activity of siRNA can be used to harness cellular machinery to destroy a corresponding sequence of mRNA that encodes a disease-causing protein. At present, the main barrier to implementing siRNA therapies in clinical practice is the lack of an effective delivery system that protects the siRNA from nuclease degradation, delivers to it to cancer cells, and releases it into the cytoplasm of targeted cancer cells, without creating adverse effects. This review provides an overview of various nanocarrier formulations in both research and clinical applications with a focus on combinations of siRNA and chemotherapeutic drug delivery systems for the treatment of multidrug resistant cancer. The use of various nanoparticles for siRNA-drug delivery, including liposomes, polymeric nanoparticles, dendrimers, inorganic nanoparticles, exosomes, and red blood cells for targeted drug delivery in cancer is discussed.
纳米载体作为药物传递系统具有广阔的应用前景，特别是在癌症治疗方面。除了通过将疏水性难溶性药物溶解在疏水性核心中来改善其药代动力学外，纳米载体还允许通过固有被动靶向现象和采用主动靶向策略进行癌症特异性联合药物传递。纳米颗粒-药物制剂可以提高局部或系统给予的药物的安全性、药代动力学特征和生物利用度，从而提高治疗效果。RNA 干扰 (RNAi) 基因沉默作为癌症治疗的一个个性化领域正在迅速发展。小干扰 RNA (siRNA) 可用于关闭特定的癌症基因，实际上是“沉默基因，沉默癌症”。siRNA 可用于沉默产生有害或异常蛋白质的特定基因。siRNA 的活性可用于利用细胞机制破坏编码致病蛋白的相应 mRNA 序列。目前，在临床实践中实施 siRNA 治疗的主要障碍是缺乏有效的传递系统，该系统可以保护 siRNA 免受核酸酶降解，将其递送至癌细胞，并将其释放到靶癌细胞的细胞质中，而不会产生不良反应。本文综述了各种纳米载体制剂在研究和临床应用中的应用，重点介绍了 siRNA 和化疗药物传递系统联合用于治疗多药耐药性癌症。讨论了各种用于 siRNA-药物传递的纳米颗粒，包括脂质体、聚合物纳米颗粒、树枝状大分子、无机纳米颗粒、外泌体和红细胞，用于癌症的靶向药物传递。
