Rapamycin as a "One-Stone-Three-Birds" Agent for Cooperatively Enhanced Phototherapies Against Metastatic Breast...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Photothermal therapy (PTT) and photodynamic therapy (PDT) offer synergistic anticancer effects but are limited by tumor resistance.
• Developing effective combination therapies is crucial for managing metastatic breast cancer.

Purpose of the Study:

• To design a core-shell nanoplatform for enhanced PTT/PDT combination therapy against metastatic breast cancer.
• To investigate the role of rapamycin (RAP) in sensitizing PTT and PDT by modulating key resistance factors.

Main Methods:

• Fabrication of a core-shell nanoplatform with chlorin e6 (Ce6) and rapamycin (RAP) core, polydopamine (PDA) shell, and PEGylation.
• Evaluation of RAP's effect on heat shock protein 70 (HSP 70) and hypoxia-inducible factor-1α (HIF-1α) expression.
• Assessment of metastasis inhibition via matrix metalloproteinases-2 (MMP-2) suppression.
• In vivo studies involving intravenous injection, tumor accumulation, dual laser irradiation, and long-term survival observation.

Main Results:

• The nanoplatform demonstrated enhanced PTT and PDT efficacy by inhibiting HSP 70 and HIF-1α expression.
• Rapamycin (RAP) effectively suppressed matrix metalloproteinases-2 (MMP-2), inhibiting cancer metastasis.
• Dual laser irradiation of the nanosystem led to complete tumor elimination and 100% survival in mice over the observation period.

Conclusions:

• The developed nanoplatform offers a promising strategy to overcome tumor resistance in phototherapies.
• This approach provides a potential solution for managing metastatic breast cancer with high efficacy and long-term survival benefits.