CaCO₃-complexed pH-responsive nanoparticles encapsulating mitoxantrone and celastrol enhance tumor chemoimmunotherapy

Area of Science:

• Oncology
• Nanotechnology
• Immunotherapy

Background:

• The tumor microenvironment (TME) is often immunosuppressive, hindering effective cancer treatment.
• Modulating the TME to enhance antitumor immunity is a key strategy in cancer immunotherapy.

Purpose of the Study:

• To design an acid-sensitive nanosystem (MCCaNPs) for delivering combined chemotherapy drugs to induce immunogenic cell death (ICD).
• To investigate the efficacy of MCCaNPs in reprogramming the TME and enhancing anti-tumor immune responses.

Main Methods:

• Developed a pH-responsive nanoplatform using CaCO3 via double emulsion method.
• Co-encapsulated mitoxantrone (MIT) and celastrol (CEL) as ICD inducers within the nanoparticles.
• Administered MCCaNPs intravenously to mice bearing tumors to assess TME modulation and anti-tumor effects.

Main Results:

• The acid-sensitive CaCO3 component of MCCaNPs consumed H+ in the acidic TME, leading to rapid release of MIT and CEL.
• MIT and CEL synergistically induced stronger ICD, evidenced by increased release of calreticulin (CRT) and high mobility group box 1 protein (HMGB1).
• MCCaNPs treatment significantly increased tumor-infiltrating cytotoxic T lymphocytes (CTLs) and prolonged survival in tumor-bearing mice.

Conclusions:

• MCCaNPs effectively reprogram the immunosuppressive TME by triggering collaborative ICD.
• This novel chemoimmunotherapy approach holds promise for boosting CTL infiltration and improving anti-cancer immunotherapy outcomes.