Jhaveri Aditi M, Torchilin Vladimir P
Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Boston, MA, USA.
Front Pharmacol. 2014 Apr 25;5:77. doi: 10.3389/fphar.2014.00077. eCollection 2014.
Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to "smart," multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.
聚合物胶束是具有核壳结构的两亲性共聚物自组装纳米结构，已被用作药物和核酸递送的通用载体。由于具有一系列有利特性，包括能够有效溶解多种难溶性药物、生物相容性、长效性、在体外和体内的高稳定性以及在血管受损的病理区域积累的能力，它们已广受欢迎。此外，通过用各种配体和细胞穿透部分对这些胶束的表面进行工程改造，可以赋予它们额外的功能，分别实现特异性靶向和细胞内积累，用造影剂加载以赋予成像能力，并引入刺激敏感基团以响应环境中的微小变化而实现药物释放。最近，设计将上述多种功能整合到单个载体中的聚合物胶束以产生“智能”多功能聚合物胶束的趋势日益增加。这种多功能胶束可被视为提高当前治疗效果的关键，目前的治疗不仅在疏水性小分子方面，而且在包括治疗性基因、抗体和小干扰RNA（siRNA）在内的生物制品方面都在稳步增加。本综述的目的是突出专门用于药物和siRNA递送的多功能聚合物胶束开发的最新进展。尽管siRNA具有巨大潜力，但其转化为临床应用一直是一项重大挑战，因为其有效递送存在生理障碍，并且缺乏安全、有效和临床适用的载体。为此，我们还讨论了多功能聚合物胶束，包括脂质基胶束，作为siRNA和药物的有前途载体的潜力和适用性。
