Department of Biological Sciences and Bioengineering, Indian Institute of Technology-Kanpur, Kanpur 208016, Uttar Pradesh, India; Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology-Kanpur, Kanpur 208016, Uttar Pradesh, India.
Carbohydr Polym. 2022 Feb 1;277:118822. doi: 10.1016/j.carbpol.2021.118822. Epub 2021 Oct 29.
Nanoparticle-based targeting of overexpressed cell-surface receptors is a promising strategy that provides precise delivery of drugs to cancer cells. In the present study, we developed highly reproducible and monodispersed, chitosan-coated (pH-responsive), doxorubicin-loaded, aptamer-mesoporous silica nanoparticle (MSN) bioconjugates for actively targeting breast cancer cells harboring overexpression of EGF receptors (EGFR/HER2). The developed targeted MSNs demonstrated higher uptake and cytotoxicity of triple negative and HER2 positive breast cancer cells when compared to non-targeted MSNs. The chitosan coating imparted pH-responsiveness and endo/lysosomal escape ability to MSNs, which augmented cytosolic delivery of an anticancer drug. Partial carboxylation of chitosan coated on MSNs allowed for a greater release of drug in a shorter duration of time while retaining pH-responsiveness and endo/lysosomal escape ability. Overall, the coating of carboxylated-chitosan over MSNs enabled tunable drug release kinetics, conjugation of aptamers (targeting agents), and endo/lysosomal escape which together significantly enhanced the efficacy of the developed drug delivery system.
基于纳米粒子的过表达细胞表面受体靶向是一种很有前途的策略，它可以将药物精确递送到癌细胞中。在本研究中，我们开发了高度重现性和单分散性的壳聚糖包覆（pH 响应性）、阿霉素负载、适体介孔硅纳米粒子（MSN）生物缀合物，用于主动靶向过表达表皮生长因子受体（EGFR/HER2）的乳腺癌细胞。与非靶向 MSN 相比，开发的靶向 MSN 表现出对三阴性和 HER2 阳性乳腺癌细胞更高的摄取和细胞毒性。壳聚糖包覆赋予 MSN pH 响应性和内体/溶酶体逃逸能力，从而增强了抗癌药物的细胞质递送。MSN 上包覆的壳聚糖部分羧化允许在更短的时间内释放更多的药物，同时保持 pH 响应性和内体/溶酶体逃逸能力。总的来说，MSN 上的羧基化壳聚糖涂层能够实现可调的药物释放动力学、适体（靶向剂）的缀合和内体/溶酶体逃逸，这些共同显著增强了开发的药物递送系统的疗效。
