“Stealth and Fully-Laden” Drug Carriers: Self-Assembled Nanogels Encapsulated with Epigallocatechin Gallate and siRNA for Drug-Resistant Breast Cancer Therapy,ACS Applied Materials & Interfaces

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“Stealth and Fully-Laden” Drug Carriers: Self-Assembled Nanogels Encapsulated with Epigallocatechin Gallate and siRNA for Drug-Resistant Breast Cancer Therapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-02-13 00:00:00 , DOI: 10.1021/acsami.7b19577
Jie Ding _{1,

2} , Tingxizi Liang ₂ , Qianhao Min ₂ , Liping Jiang ₂ , Jun-Jie Zhu ₂

Affiliation

For codelivery of therapeutic genes and chemical agents in combined therapy, the ideal drug delivery system entails high-capacity and low-body toxicity carriers, allowing adequate drug dose for tumor regions while yielding low residues in normal tissues. To augment the gene/drug load capacity and circumvent the potential toxicity brought by traditional inorganic and polymeric nanocarriers, a “stealth” carrier was herein designed in a simple self-assembly of (−)-epigallocatechin-3-O-gallate (EGCG) and small interfering RNA (siRNA) by recruiting protamine as a biodegradable medium for the treatment of drug-resistant triple-negative breast cancer. In the self-assembled nanogel, entrapped siRNA played a central role in sensitizing the tumor response to EGCG-involved chemotherapy, and the positively charged protamine served as the assembly skeleton to fully accommodate gene and drug molecules and minimize the factors causing side effects. As compared to stand-alone chemotherapy with EGCG, the multicomponent nanogel revealed a 15-fold increase in the cytotoxicity to drug-resistant MDA-MB-231 cell line. Moreover, equipped with hyaluronic acid and tumor-homing cell-penetrating peptide as the outmost targeting ligands, the siRNA- and EGCG-loaded nanogel demonstrates superior selectivity and tumor growth inhibition to free EGCG in xenograft MDA-MB-231 tumor-bearing mice. Meanwhile, thanks to the acknowledged biosafety of protamine, little toxicity was found to normal tissues and organs in the animal model. This gene/drug self-assembly caged in a biodegradable carrier opens up an effective and secure route for drug-resistant cancer therapy and provides a versatile approach for codelivery of other genes and drugs for different medical purposes.

中文翻译：

“隐身和全载”药物载体：表没食子儿茶素没食子酸酯和siRNA封装的自组装纳米凝胶，用于抗药性乳腺癌治疗

对于联合治疗中的治疗基因和化学试剂的代码传递，理想的药物传递系统需要高容量和低体毒性的载体，从而为肿瘤区域提供足够的药物剂量，同时在正常组织中产生低残留物。为了增加基因/药物的负载能力并避免传统的无机和聚合物纳米载体带来的潜在毒性，本文在（-）-epigallocatechin-3- O的简单自组装中设计了“隐形”载体。-gallate（EGCG）和小干扰RNA（siRNA），通过募集鱼精蛋白作为可生物降解的介质来治疗耐药性三阴性乳腺癌。在自组装的纳米凝胶中，截留的siRNA在使肿瘤对EGCG参与的化疗反应敏感中起着核心作用，而带正电荷的鱼精蛋白可作为组装骨架，以完全容纳基因和药物分子并最小化引起副作用的因素。与单独的EGCG化疗相比，多组分纳米凝胶对耐药MDA-MB-231细胞系的细胞毒性提高了15倍。此外，由于透明质酸和肿瘤归巢细胞穿透肽是最主要的靶向配体，载有siRNA和EGCG的纳米凝胶在带有异种移植物的MDA-MB-231荷瘤小鼠中显示出对游离EGCG的优异选择性和肿瘤生长抑制作用。同时，由于鱼精蛋白的公认生物安全性，在动物模型中对正常组织和器官的毒性很小。笼罩在生物可降解载体中的这种基因/药物自组装为耐药性癌症治疗开辟了一条有效而安全的途径，并为其他基因和药物的不同医疗目的的代码传递提供了一种通用的方法。

更新日期：2018-02-13

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