KCl Nanoparticles as Potential Inducer of Immunogenic Cell Death for Cancer Immunotherapy

Immunogenic cell death (ICD) is a promising cancer immunotherapy by inducing antigen-presenting cell maturation. Many inorganic nanomodulators have been developed for cancer therapy via ion overload, and their ICD-inducing properties have also been explored for immunotherapy. Here, we report a potassium chloride nanoparticle (PCNP)-loaded poly(lactic-co-glycolic acid) nanoparticle coated with cancer cell membrane (PC@P-CCM) for cancer therapy. Through cancer cell membrane (CCM)-achieved surface functionalization, the homotypic targeting behaviors of PC@P-CCM are dramatically enhanced. Once internalized by cancer cells, the PC@P-CCM could be degraded in acidic lysosomes, thus releasing K+ and Cl– ions. These ions can change the osmotic pressure of cancer cells, causing a hypertonic state in the cancer cells in a short time and leading to the rupture and death of cancer cells. Furthermore, these ions can stimulate cancer cells to secrete adenosine triphosphate (ATP) and high mobility group box 1 (HMGB-1); meanwhile, calreticulin (CRT) showed increased presentation on the surface of cancer cells, which can further induce dendritic cell maturation and promote the immunotherapy. This work provides a new perspective on KCl nanoparticle-based cancer immunotherapy.