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

Immunogenic cell death (ICD) is a promising cancer immunotherapyby inducing antigen-presenting cell maturation. Many inorganic nanomodulatorshave been developed for cancer therapy via ion overload, and theirICD-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)-achievedsurface functionalization, the homotypic targeting behaviors of PC@P-CCMare dramatically enhanced. Once internalized by cancer cells, thePC@P-CCM could be degraded in acidic lysosomes, thus releasing K+ and Cl- ions. These ions can change theosmotic pressure of cancer cells, causing a hypertonic state in thecancer cells in a short time and leading to the rupture and deathof cancer cells. Furthermore, these ions can stimulate cancer cellsto secrete adenosine triphosphate (ATP) and high mobility group box1 (HMGB-1); meanwhile, calreticulin (CRT) showed increased presentationon the surface of cancer cells, which can further induce dendriticcell maturation and promote the immunotherapy. This work providesa new perspective on KCl nanoparticle-based cancer immunotherapy.