Subcellular-Targeted Near-Infrared-Responsive Nanomedicine with Synergistic Chemo-photothermal Therapy against...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Multidrug resistance (MDR) significantly limits the efficacy of conventional cancer treatments.
• Combining chemotherapy with photothermal therapy (PTT) presents a promising strategy to overcome MDR.
• Developing targeted nanomedicines is crucial for efficient drug delivery and therapeutic outcomes.

Purpose of the Study:

• To develop a subcellular-targeted, near-infrared (NIR)-responsive nanomedicine for enhanced cancer therapy.
• To create a novel photothermal agent with improved stability and efficiency for MDR cancer treatment.
• To investigate the synergistic effects of chemotherapy and PTT mediated by the nanomedicine.

Main Methods:

• Synthesis of a multifunctional nanomedicine (Fe3O4@PDA-TPP/S2-PEG-hyd-DOX, Fe3O4-ATSPD) incorporating magnetic nanoparticles, photothermal agent, and chemotherapy drug (DOX).
• Utilized magnetic targeting and the enhanced permeability and retention (EPR) effect for tumor accumulation.
• Investigated NIR-induced photothermal effect, drug release kinetics, subcellular targeting, and therapeutic efficacy in MDR cancer models.

Main Results:

• The Fe3O4-ATSPD nanomedicine exhibited high stability in circulation and efficient tumor accumulation.
• NIR irradiation triggered a potent photothermal effect, leading to decreased mitochondrial membrane potential.
• Subcellularly targeted drug release under acidic endosomal/lysosomal conditions induced DNA damage and apoptosis in MDR cancer cells.

Conclusions:

• The developed subcellular-targeted NIR-responsive nanomedicine effectively integrates diagnosis and therapy for enhanced MDR cancer treatment.
• The combination of chemotherapy and PTT via this nanomedicine offers a significant advancement in overcoming drug resistance.
• This approach holds potential for improving clinical outcomes in patients with multidrug-resistant cancers.