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

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Thermosensitive liposomes (TSLs) offer controlled drug release but struggle with in vivo stability.
• Hyperthermia (HT) enhances TSL drug release, but physiological temperatures pose challenges.
• Doxorubicin (DOX) is a potent chemotherapy drug with significant cardiotoxicity.

Purpose of the Study:

• To develop polymer-based thermosensitive liposomes (P-TSLs) for improved in vivo stability and tumor-specific doxorubicin delivery.
• To evaluate the thermo-sensitivity, drug release kinetics, and cellular uptake of the novel P-TSLs.
• To assess the in vivo efficacy, biodistribution, and biocompatibility of P-TSLs for cancer treatment.

Main Methods:

• Synthesis of p(NIPAM-r-HPMA) and p(HPMA-r-APMA) polymers using RAFT technique.
• Postinsertion of p(NIPAM-r-HPMA) into thermosensitive liposomes (TSLs) to create P-TSLs.
• In vitro and in vivo studies including drug release assays, cellular uptake, tumor spheroid penetration, and animal model experiments.

Main Results:

• P-TSLs exhibited a phase transition temperature of ~42 °C with rapid DOX release (~70% in 1 min) under HT.
• P-TSLs demonstrated enhanced stability at 37 °C and significantly increased DOX cellular uptake under HT compared to TSLs.
• In vivo studies showed enhanced DOX deep penetration, prolonged blood circulation, and reduced cardiotoxicity with CY-P-TSLs and HT.

Conclusions:

• Developed P-TSLs offer a promising platform for tumor-specific drug delivery with enhanced stability and controlled release.
• P-TSLs combined with hyperthermia significantly improve drug efficacy and reduce systemic toxicity.
• The novel P-TSL system represents a reliable thermosensitive drug carrier for advanced cancer therapy.