Synergistic Chemo-Immunotherapy Using pH-Responsive Nanoparticles in Breast Cancer Treatment: In Vitro and In Vivo...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Nanotechnology

Background:

• The tumor microenvironment (TME) significantly influences tumor progression and survival.
• Tumor-associated macrophages (TAMs) in the TME create an immunosuppressive environment, promoting tumor growth and resistance.
• Combining chemotherapy with immunomodulatory agents offers therapeutic potential by reprogramming TAMs.

Purpose of the Study:

• To develop pH-responsive nanoparticles (PHNPs) for targeted delivery of paclitaxel (PTX) and resiquimod (RSQ).
• To evaluate the efficacy of PHNP-mediated combined chemo-immunotherapy against breast cancer.

Main Methods:

• Engineered pH-responsive nanoparticles (PHNPs) using star-shaped PLGA conjugated with polyhistidine.
• Loaded PHNPs with paclitaxel (PTX) and resiquimod (RSQ) for combined chemo-immunotherapy.
• Conducted in vitro studies on drug release, tumor spheroid penetration, and cytotoxicity.
• Performed in vivo studies in a mouse orthotopic breast cancer model to assess drug delivery, anti-tumor efficacy, and metastasis inhibition.

Main Results:

• PHNPs demonstrated enhanced drug release at pH 6.4 and improved penetration in tumor spheroids.
• In vitro studies showed increased cytotoxic efficacy against breast cancer cells and macrophage activation.
• In vivo studies confirmed increased plasma AUC and tumor drug delivery, leading to enhanced anti-tumor effectiveness.
• PHNP treatment elevated intratumoral ROS and apoptosis, and significantly inhibited lung metastasis.

Conclusions:

• The developed PHNPs effectively deliver a combination of PTX and RSQ to the tumor site.
• Combined chemo-immunotherapy using PHNPs shows significant potential for treating breast cancer.
• PHNP-mediated therapy demonstrates promising anti-tumor activity and metastasis inhibition.