Supramolecularly engineered bacteria mediated calcium overload and immunotherapy of tumors
Beibei Xie, Lin Dong, Leo D. Wang, Ruibing Wang, Chunlai Li
Abstract
Intracellular Ca 2+ nanogenerators, such as calcium carbonate, calcium peroxide, and calcium phosphate nanoparticles, have shown promise in calcium overload-mediated tumor therapy.However, their effectiveness is often hampered by poor targeting, low accumulation, and limited penetration into tumor cells, leading to suboptimal therapeutic outcomes.This strategy aims to achieve synergistic Ca 2+ overload and immunotherapy of tumors.Methods: A supramolecular conjugate of engineered living bacteria (facultative anaerobic Salmonella typhimurium VNP20009, VNP) with CaCO3 nanoparticles was developed for targeted delivery of curcumin-loaded CaCO3 into tumors.Results: Both CaCO3 nanoparticles and the loaded Ca 2+ efflux inhibiting agent, curcumin (CUR), demonstrated significant enhancement of intracellular Ca 2+ overload, resulting in apoptosis of tumor cells via mitochondrial dysfunction.Moreover, VNP exhibited excellent tumor-targeting ability, colonization in tumor tissues, and anticancer activity with minimal side effects. Conclusion:The conjugate of VNP and CaCO3 not only enhances the efficiency of common cancer treatments but also synergizes Ca 2+ overload with cancer immunotherapy, thereby offering a promising approach for improving therapeutic outcomes in cancer treatment.