Bioinspired mimics: Self-assembly of redox-activated phosphorylcholine–based biodegradable copolymers for enhancing antitumor efficiency

Highlights: • Reduction-activated PCL-ss-PMPC was successfully designed and synthesized. • The biomimicking polymeric micelles achieved long blood transportation, faster cellular uptake and accelerated release in cytoplasm. • The DOX-loaded micelles considerably reduce side effects and systematic toxicity. - Abstract: With the purpose of reducing side effects in anticancer therapy, the micelles of a novel reduction-activated copolymer with biomimicking phosphorylcholine, poly(ε-caprolactone)-ss-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL-ss-PMPC) are developed. The well-suitable nanosize of micelles with good physiological stability (approximately 50 nm, 2.5 μg/mL) can be quickly internalized into cells due to bioinspired phosphorylcholine property and mainly located in endo/lysosomes. The reduction response of micelles is confirmed by size change and accelerated drug release under reducing environment, proved as better anticancer efficacy in comparison to insensitive micelles. Pharmacokinetics and in vivo studies demonstrate that redox-activated polymeric micelles can prolong blood transportation, facilitate passive target and accumulate in tumor site, and prompt drug release in cytoplasmic redox environment, behaving as much better antitumor efficiency than control and positive DOX·HCl groups. More importantly, the DOX-loaded micelles considerably reduce side effects and systematic toxicity. Therefore, this work fabricated an innovative bioinspired nanosystem via a facile strategy to achieve effective anticancer therapy.