A Programmable Calcification Nanoplatform for Loco-Regional Calcification-Immune Hepatocellular Carcinoma Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Tumor calcification is a promising cancer treatment strategy.
• Efficient biomineralization with antitumor effects is challenging.

Purpose of the Study:

• Develop a programmable calcification nanoplatform (CaIM) for cancer therapy.
• Investigate the mechanisms of CaIM-induced tumor calcification and antitumor effects.

Main Methods:

• In situ growth of calcium peroxide (CaO2) on black phosphorus (BP) nanosheets, followed by hyaluronic acid encapsulation.
• Utilized multi-omics profiling to identify key molecular mediators.
• Assessed therapeutic efficacy through in vitro and in vivo experiments.

Main Results:

• CaIM achieved uniform CaO2 anchoring and synchronized release of therapeutic ions and H2O2.
• CaIM induced intracellular calcium overload, oxidative stress, and mitochondrial dysfunction, leading to cell death and CT-visible calcification.
• Identified MCOLN2 as a key regulator of active biomineralization.
• Demonstrated CaIM's ability to reshape the tumor microenvironment, promoting anti-tumor immunity.

Conclusions:

• The developed CaIM nanoplatform offers a novel approach for cancer therapy by combining targeted calcification, oxidative stress, and immune activation.
• This calcium signaling-driven strategy provides a robust foundation for developing advanced calcification-based cancer treatments.