College of Materials Science and Engineering, Nanjing Tech University , 30 South Puzhu Road, Nanjing 211816, P. R. China.
ACS Appl Mater Interfaces. 2017 Mar 22;9(11):9402-9415. doi: 10.1021/acsami.6b16689. Epub 2017 Mar 7.
RNA interference (RNAi) has a great promise in treating various acquired and hereditary diseases. However, it remains highly desirable to develop new delivery system to circumvent complex extra- and intracellular barriers for successful clinical translation. Here, we report on a versatile polymeric vector, bioreducible fluorinated peptide dendrimers (BFPD), for efficient and safe small interfering RNA (siRNA) delivery. In virtue of skillfully integrating all of the unique advantages of reversible cross-linking, fluorination, and peptide dendrimers, this novel vector can surmount almost all extra- and intracellular barriers associated with local siRNA delivery through highly improved physiological stability and serum resistance, significantly increased intratumoral enrichment, cellular internalization, successful facilitation of endosomal escape, and cytosolic siRNA release. BFPD polyplexes, carrying small interfering vascular endothelial growth factor (siVEGF), demonstrated excellent VEGF silencing efficacy (∼65%) and a strong capability for inhibiting HeLa cell proliferation. More importantly, these polyplexes showed superior performance in long-term enrichment in the tumor sites and had a high level of tumor growth inhibition. Furthermore, these polyplexes not only exhibited excellent in vivo antitumor efficacy but also demonstrated superior biocompatibility, compared with LPF2000, both in vivo and in vitro. These findings indicate that BFPD is an efficient and safe siRNA delivery system and has remarkable potential for RNAi-based cancer treatment.
RNA 干扰 (RNAi) 在治疗各种获得性和遗传性疾病方面具有巨大的潜力。然而，开发新的传递系统以克服复杂的细胞外和细胞内屏障，以实现成功的临床转化，仍然是非常需要的。在这里，我们报告了一种多功能聚合物载体，生物还原型氟代肽树突 (BFPD)，用于高效和安全的小干扰 RNA (siRNA) 传递。由于巧妙地整合了可逆交联、氟化和肽树突的所有独特优势，这种新型载体可以克服与局部 siRNA 传递相关的几乎所有细胞外和细胞内屏障，通过高度提高的生理稳定性和血清抗性、显著增加的肿瘤内富集、细胞内内化、成功促进内涵体逃逸和细胞质 siRNA 释放。携带小干扰血管内皮生长因子 (siVEGF) 的 BFPD 超分子复合物表现出优异的 VEGF 沉默效果（约 65%）和抑制 HeLa 细胞增殖的强大能力。更重要的是，这些超分子复合物在肿瘤部位的长期富集中表现出优异的性能，并且具有高水平的肿瘤生长抑制作用。此外，与 LPF2000 相比，这些超分子复合物不仅在体内和体外都表现出优异的抗肿瘤疗效，而且表现出优异的生物相容性。这些发现表明，BFPD 是一种高效、安全的 siRNA 传递系统，具有基于 RNAi 的癌症治疗的巨大潜力。
