Small Delivery Vehicles of siRNA for Enhanced Cancer Targeting,Biomacromolecules

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Small Delivery Vehicles of siRNA for Enhanced Cancer Targeting
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-06-04 00:00:00 , DOI: 10.1021/acs.biomac.8b00546
Hyun Jin Kim ₁ , Yu Yi _{2,

3} , Ahram Kim ₄ , Kanjiro Miyata ₂

Affiliation

Small interfering RNA (siRNA) drugs have been considered to treat various diseases in major organs. However, siRNA drugs developed for cancer therapy are hindered from proceeding to the clinic. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic siRNA delivery to solid tumors. Most of these delivery vehicles do not generate small particle sizes and pharmacokinetics required for accumulation in target cancer cells compared with clinically tested anticancer drug-loaded polymeric micelles. This review describes the significance of small, long-circulating vehicles for efficient delivery of siRNA to cancer tissues via the enhanced permeability and retention (EPR) effect. We summarize recent biological evidence that supports the size effect of delivery vehicles in tumor microenvironments and introduce promising strategies for the construction of small vehicles with sizes of 10–50 nm. We then discuss the feasibility of these delivery vehicles with respect to translation to clinical trials.

中文翻译：

siRNA的小型运载工具可增强癌症靶向性

小型干扰RNA（siRNA）药物已被认为可以治疗主要器官的各种疾病。但是，为癌症治疗而开发的siRNA药物无法进入临床。迄今为止，已经从阳离子脂质，聚合物和/或无机纳米颗粒开发了各种递送制剂，用于全身性siRNA递送至实体瘤。与经过临床测试的载有抗癌药物的聚合物胶束相比，这些传递载体中的大多数都不会产生在靶癌细胞中积累所需的小粒径和药代动力学。这篇综述描述了小而长循环的载体对于通过增强的通透性和保留（EPR）效应将siRNA有效递送至癌症组织的重要性。我们总结了最近的生物学证据，这些证据支持肿瘤微环境中运载工具的大小效应，并介绍了构建10–50 nm大小的小型运载工具的有前途的策略。然后，我们将讨论这些交付工具在翻译成临床试验方面的可行性。

更新日期：2018-06-04

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