GSH-Activatable NIR Nanoplatform with Mitochondria Targeting for Enhancing Tumor-Specific Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Developing targeted therapies for photodynamic therapy (PDT) is crucial for improving efficacy and reducing side effects.
• Tumor-specific signals and stimuli-responsive materials are key for precise drug delivery.

Purpose of the Study:

• To construct a nanoplatform for glutathione (GSH)-activatable and mitochondria-targeted photodynamic therapy (PDT).
• To achieve imaging-guided, tumor-specific PDT with enhanced antitumor efficacy and minimal side effects.

Main Methods:

• Synthesized a GSH-activatable pro-photosensitizer (di-cyanine, DCy7) linked by a disulfide bond.
• Encapsulated DCy7 within pH-responsive polymer (POEGMA-b-PDPA) to form P@DCy7 nanoparticles.
• Investigated nanoparticle dissociation, drug release, GSH activation, mitochondrial targeting, and selective phototoxicity in vitro and in vivo.

Main Results:

• P@DCy7 nanoparticles demonstrated pH-responsive dissociation and GSH-triggered release and activation of DCy7 in cancer cells.
• The nanoparticles selectively targeted cancer cell mitochondria, leading to enhanced phototoxicity.
• Selective phototoxicity against tumor cells (HepG2, 4T1) over normal cells (BEAS-2B) was observed in vitro.
• Enhanced PDT efficacy was confirmed in tumor-bearing mice, with GSH consumption aiding the process.

Conclusions:

• P@DCy7 nanoparticles offer a promising nanoplatform for precise, organelle-targeted PDT.
• The developed system enables accurate and highly efficient tumor-specific PDT with reduced side effects.
• This strategy provides a new avenue for smart photosensitizer development in cancer therapy.