Navarro Gemma, Pan Jiayi, Torchilin Vladimir P
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University , Boston, Massachusetts 02115, United States.
Mol Pharm. 2015 Feb 2;12(2):301-13. doi: 10.1021/mp5007213. Epub 2015 Jan 12.
Gene therapy represents a potential efficient approach of disease prevention and therapy. However, due to their poor in vivo stability, gene molecules need to be associated with delivery systems to overcome extracellular and intracellular barriers and allow access to the site of action. Cationic polymeric nanoparticles are popular carriers for small interfering RNA (siRNA) and DNA-based therapeutics for which efficient and safe delivery are important factors that need to be optimized. Micelle-like nanoparticles (MNP) (half micelles, half polymeric nanoparticles) can overcome some of the disadvantages of such cationic carriers by unifying in one single carrier the best of both delivery systems. In this review, we will discuss how the unique properties of MNP including self-assembly, condensation and protection of nucleic acids, improved cell association and gene transfection, and low toxicity may contribute to the successful application of siRNA- and DNA-based therapeutics into the clinic. Recent developments of MNP involving the addition of stimulus-sensitive functions to respond specifically to pathological or externally applied "triggers" (e.g., temperature, pH or enzymatic catalysis, light, or magnetic fields) will be discussed. Finally, we will overview the use of MNP as two-in-one carriers for the simultaneous delivery of different agents (small molecules, imaging agents) and nucleic acid combinations.
基因治疗是一种潜在的高效疾病预防和治疗方法。然而,由于基因分子在体内稳定性较差,需要与递送系统结合,以克服细胞外和细胞内的障碍,并使其能够到达作用部位。阳离子聚合物纳米颗粒是用于小干扰RNA(siRNA)和基于DNA的治疗药物的常用载体,对于这些药物而言,高效且安全的递送是需要优化的重要因素。类胶束纳米颗粒(MNP)(半胶束、半聚合物纳米颗粒)可以通过在单个载体中结合两种递送系统的最佳特性,克服此类阳离子载体的一些缺点。在本综述中,我们将讨论MNP的独特性质,包括自组装、核酸的凝聚和保护、改善的细胞结合和基因转染以及低毒性,这些性质如何有助于基于siRNA和DNA的治疗药物成功应用于临床。还将讨论MNP的最新进展,包括添加刺激敏感功能以特异性响应病理或外部施加的“触发因素”(例如温度、pH或酶催化、光或磁场)。最后,我们将概述MNP作为二合一载体同时递送不同药物(小分子、成像剂)和核酸组合的应用情况。
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