NIR Activated Upper Critical Solution Temperature Polymeric Micelles for Trimodal Combinational Cancer Therapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Balancing drug efficacy and side effects in cancer therapy remains a challenge.
• Nanomedicine offers improved drug circulation and reduced toxicity.
• Multimodal therapies are emerging to overcome treatment limitations.

Purpose of the Study:

• To construct dual-responsive polymeric micelles for combined chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT).
• To develop a nanomedicine delivery system utilizing an upper critical solution temperature (UCST) polymer for targeted cancer treatment.
• To investigate the efficacy of these micelles in vitro and in vivo.

Main Methods:

• Self-assembly of an amphiphilic block copolymer P(AAm-co-AN)-b-PEI-ss-PEG-FA into polymeric micelles.
• Encapsulation of doxorubicin (DOX) and photosensitizer ALS into micelles (DOX&ALS@MFM).
• Evaluation of micelle targeting, drug release, photothermal conversion, reactive oxygen species generation, and anti-tumor effects.

Main Results:

• DOX&ALS@MFM micelles showed targeted aggregation at tumor sites via folate targeting and EPR effect.
• Intracellular glutathione (GSH) and near-infrared (NIR) light triggered micelle disassembly and drug release.
• Demonstrated efficient photothermal conversion, singlet oxygen generation, and significant tumor growth inhibition in vitro and in vivo.

Conclusions:

• The developed UCST-based polymeric micelles offer a promising strategy for triple-modal tumor therapy.
• This nanomedicine approach enhances drug delivery and therapeutic outcomes while minimizing toxicity.
• The study highlights the potential of UCST polymers in advanced biomedical applications for cancer treatment.