Quick-Responsive Polymer-Based Thermosensitive Liposomes for Controlled Doxorubicin Release and Chemotherapy

Thermosensitive liposomes (TSLs) have been widely investigated for controlled drug release at specific pathophysiological sites. Although excellent thermo-sensitivity under hyperthermia (HT) was already realized for TSLs, their in vivo stability under physiological temperature still remains challenging. To overcome this limitation, optimized polymer-based thermosensitive liposomes (P-TSLs) with good thermo-sensitivity as well as satisfactory in vivo stability were developed in this study for tumor-specific controlled delivery of doxorubicin (DOX). In particular, polymers including p(NIPAM-r-HPMA) and p(HPMA-r-APMA) were successfully synthesized based on a reversible addition–fragmentation chain transfer (RAFT) technique. Next, thermosensitive polymer p(NIPAM-r-HPMA) was first proposed to be inserted into the lipid bilayer of TTSL by a postinsertion method. The resulting P-TTSL had a phase transition temperature (Tm) of around 42 °C and displayed excellent thermo-sensitivity under HT: nearly 70% of DOX was...