NIR-Responsive Polypeptide Nanocomposite Generates NO Gas, Mild Photothermia, and Chemotherapy to Reverse...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Therapy

Background:

• Multidrug resistance (MDR) in cancer, often due to P-glycoprotein (P-gp) overexpression, significantly limits chemotherapy efficacy.
• Current polypeptide nanomedicines face challenges in clinical translation due to MDR.
• Developing strategies to overcome MDR is crucial for improving cancer treatment outcomes.

Purpose of the Study:

• To develop a novel polypeptide nanocomposite (PNOC-PDA) capable of overcoming MDR.
• To integrate chemotherapy (CT), nitric oxide (NO) gas delivery, and photothermal therapy (PTT) for synergistic cancer treatment.
• To investigate the efficacy of this triple therapy in reversing MDR and eradicating cancer cells.

Main Methods:

• Fabrication of PNOC-PDA nanocomposite with NO gas delivery and photothermal conversion properties.
• In vitro evaluation using MCF-7/ADR cells to assess MDR reversal and cancer cell killing via MTT, Western blot, flow cytometry, and confocal microscopy.
• In vivo studies involving intravenous injection of PNOC-PDA/DOX and near-infrared irradiation for tumor ablation in a mouse model.

Main Results:

• PNOC-PDA demonstrated synergistic effects in reversing MDR and killing MCF-7/ADR cells in vitro.
• P-glycoprotein (P-gp) expression was significantly downregulated to 46% in treated cells.
• A single intravenous injection and near-infrared irradiation achieved complete tumor ablation in vivo without recurrence or significant side effects.

Conclusions:

• The developed PNOC-PDA nanocomposite effectively overcomes MDR by combining CT, NO gas therapy, and mild PTT.
• This versatile platform offers a promising new strategy for reversing tumor MDR and enhancing cancer therapy.
• The study highlights a novel approach for fabricating NIR-responsive polypeptide nanocomposites with combined therapeutic functionalities.