Construction of a Drug Delivery System via pH-Responsive Polymeric Nanomicelles Containing Ferrocene for DOX Release and Enhancement of Therapeutic Effects

We report an amphiphilic block copolymer via poly(ethylene glycol) methyl ether-D-labile-poly(caprolactone)-ferrocene (mPEG-D-labile-PCL-Fc) to deliver anticancer drug doxorubicin (DOX). Lipase Novozyme-435 was used as a catalyst for ring-opening polymerization with epsilon-caprolactone, and an acid-sensitive Schiff base was used to connect the hydrophilic and hydrophobic parts; the ferrocene provided ferrous ions and was introduced at the end of the amphiphilic copolymer. The resulting copolymers were characterized by H-1 NMR/C-13 NMR and could be self-assembled in an aqueous solution to form nanomicelles with PCL-Fc as a hydrophobic core and mPEG as a hydrophilic shell. Transmission electron microscopy showed that the micelles were spherical and nanosized before and after DOX loading. The blank micelles also showed good biocompatibility. The drug-loaded polymeric nanomicelles exhibited a positive anticancer effect relative to the copolymers without ferrocene; the therapeutic effect of drug-loaded micelles containing ferrocene was more obvious. In vitro drug release results also showed that the polymer had a good pH response. Confocal microscopy also showed that polymeric micelles can effectively deliver and release the drug; the polymer containing ferrocene also leads to significantly improved ROS levels in tumor cells. Ferrocene can effectively and synergistically inhibit tumor cells with DOX.

Automated summary

A newly prepared amphiphilic block copolymer nanomicelle successfully delivered the anticancer drug DOX to tumor sites, demonstrating good drug release performance and anticancer effects. Furthermore, these nanomicelles showed significantly improved therapeutic effects in treating tumor cells with the introduction of ferrocene.