Chitosan-coated PLA/poloxamer nanoparticles stimulate immunologic cancer cell death and synergistic chemo-immunotherapeutic efficacy

Abstract

Cancer, a key factor in declining global life expectancy, has driven the integration of chemotherapy and immunotherapy to address multidrug resistance and influence the tumor microenvironment. We developed a novel vaccine delivery carrier, a chitosan-coated polylactic acid/poloxamer nanoparticle (CPP NP), designed to co-encapsulate an anticancer drug and antigen without any chemical conjugation process, enabling effective and synergistic cancer chemo-immunotherapy. The CPP NP achieved synergistic efficacy through paclitaxel (PTX), an immunogenic cell death-inducing chemotherapeutic agent; ovalbumin (OVA), which promotes dendritic cell maturation; and enhanced cellular uptake facilitated by chitosan. The PTX and OVA-loaded CPP NPs (PTX/OVA@CPP NPs) were stable in PBS for four weeks and resuspended well after lyophilization without any cryoprotectants. Moreover, PTX and OVA from the NPs exhibited a sustained release rate and pH-responsive release pattern within different cellular microenvironments. Importantly, PTX@CPP NPs exhibited much higher anticancer efficacy across various cancer cell lines, even multidrug-resistant cells, compared to free PTX and PTX@PP NPs without the chitosan coating. In antigen-presenting cells, OVA@CPP NPs led to higher IL-2 secretion and cellular uptake compared to free OVA and OVA@PP NPs. Furthermore, in a tumor-bearing mouse model, PTX/OVA@CPP NPs exhibited strong synergistic tumor suppression and triggered OVA antigen-specific responses, promoting an antitumor immune response. These findings demonstrate that PTX/OVA@CPP NPs show potential as new chemo-immunotherapeutic agents for effective cancer treatment.