Redox-Sensitive multifunctional hyaluronic acid-based nanomicelles with Fine-controlled anticancer drug release

Abstract

A significant contributor to cancer-related death globally is metastatic breast cancer. To reduce death rates, tumor-specific penetration and triggered drug release are crucial. Herein, targeted intracellular doxorubicin (Dox) delivery system was effectively prepared based on redox-sensitive hyaluronic acid-palmitoyl (HA-ss-PA) copolymers. The amphiphilic copolymers self-assembled into nano and showed outstanding drug-loading capacities and encapsulation efficiency for Dox. Micelles were stable under physiological conditions, but they quickly disintegrated in the presence of a reducing agent. The intracellular location of the fluorescent probe rhodamine b demonstrated that HA-ss-PA micelles are an efficient approach for drug delivery in breast cancer cells. Based on flow cytometry and live/dead assay, observations indicated that micelles induce apoptosis in both MCF-7 and MDA-MB-231 cells. In vivo evaluation in tumor-bearing mice confirmed that HA-ss-PA micelles exhibited excellent tumor-targeting activity. These findings imply that redox-sensitive HA-ss-PA micelles are promising candidates for use as intracellular delivery systems for hydrophobic anti-cancer drugs.