A mitochondria-targeted anticancer nanoplatform with deep penetration for enhanced synergistic sonodynamic and...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Sonodynamic therapy (SDT) induces tumor cell apoptosis via reactive oxygen species (ROS), but faces limitations in sonosensitizer enrichment and tumor penetration.
• Targeting mitochondria and blocking tumor energy supply are potential strategies to enhance cancer treatment efficacy.

Purpose of the Study:

• To develop core/shell polylactic-co-glycolic acid (PLGA) nanoparticles for synergistic sonodynamic and starvation therapy.
• To achieve deep tumor penetration and selective mitochondrial targeting for enhanced cancer treatment.
• To utilize nanoparticles as imaging agents for monitoring and guiding cancer therapy.

Main Methods:

• Synthesis of core/shell PLGA nanoparticles encapsulating glucose oxidase (GOx) in the core and hematoporphyrin monomethyl ether (HMME) and IR780 in the shell.
• Evaluation of nanoparticle accumulation in tumor tissues, deep tumor penetration, and mitochondrial targeting.
• Assessment of synergistic sonodynamic and starvation therapy efficacy, including tumor growth inhibition.
• Utilizing nanoparticles as photoacoustic (PA) and fluorescent (FL) imaging contrast agents.

Main Results:

• The developed nanoparticles demonstrated deep tumor penetration and selective accumulation in cancer cell mitochondria.
• Synergistic sonodynamic and starvation therapy resulted in a significant reduction in tumor growth (4.7-fold lower than control).
• The nanoparticles functioned effectively as PA/FL imaging agents for therapy monitoring and guidance.

Conclusions:

• Core/shell PLGA nanoparticles offer a promising strategy for synergistic sonodynamic and starvation cancer therapy.
• Mitochondrial targeting and energy blockade enhance the efficacy of sonodynamic therapy.
• These nanoparticles provide a dual-modal imaging and therapeutic platform for improved cancer treatment.