Enzyme/pH Dual-Responsive Engineered Nanoparticles for Improved Tumor Immuno-Chemotherapy

Area of Science:

• Oncology
• Nanotechnology
• Immunotherapy

Background:

• Immune checkpoint blockade (ICB) combined with chemotherapy offers enhanced efficacy but faces challenges.
• Chemotherapy's lack of tumor specificity causes adverse reactions.
• Monoclonal antibodies have limited tissue penetration and cause immune-related adverse events.

Purpose of the Study:

• To develop a dual-responsive nanoparticle (CMFn@OXA) for targeted cancer therapy.
• To achieve controlled release of anti-PD-L1 peptide and oxaliplatin.
• To overcome limitations of traditional combination therapies.

Main Methods:

• Engineered ferritin-based nanoparticles (CMFn@OXA) were designed.
• Dual-responsive drug release triggered by tumor microenvironment (MMP-2/9 and acidic lysosomes).
• Evaluation of tumor accumulation, drug release, therapeutic efficacy, and biocompatibility in vivo.

Main Results:

• CMFn@OXA demonstrated tumor-specific accumulation and controlled release of anti-PD-L1 peptide and oxaliplatin.
• The nanoparticle effectively blocked PD-1/PD-L1 interaction and delivered oxaliplatin intracellularly.
• CMFn@OXA significantly inhibited tumor growth and extended survival in mice with excellent biocompatibility.

Conclusions:

• CMFn@OXA represents a promising dual-responsive nanomedicine for cancer immunotherapy.
• This strategy enhances synergistic effects of chemotherapy and ICB.
• CMFn@OXA offers a potential solution to improve safety and efficacy in cancer treatment.