pH-responsive core-shell nanogels induce in situ antigen production for cancer treatment

Chemo-immunotherapy has the superiority of remedying malignant and metastatic tumors, and acquiring better therapeutic effect as well as prognosis than monotherapy. Herein, we report a kind of pH-responsive core-shell nanoparticles to achieve the co-delivery of oxaliplatin intermediate (oxa im) (HCLO NPs) and cytosine-guanine containing oligodeoxynucleotides (CpG) for cancer treatment. The nanoparticles comprise the core of lipidcoated calcium carbonate and the outer layer of hyaluronic acid (HA), providing itself with pH-sensitivity and great biocompatibility. When intratumorally injected, oxa im induces in situ antigen production through immunogenic cell death (ICD) while CpG enhances antigen presentation and facilitates the generation of cytotoxic T lymphocytes (CTLs). In vitro, the HCLO NPs enhanced the toxicity of oxa im to CT26 cells and upregulated the expression of calreticulin (CRT, "eat me" signal). What's more, oxaliplatin precursor (oxa pre) directly upregulated CD47 ("don't eat me" signal) expression in CT26 cells, while being encapsulated into NPs attenuated this upregulation. In vivo, HCLO NPs elicited prominent anti-tumor immunity and abscopal effect, meanwhile significantly increased the infiltration of CD8+ T cells in the tumor microenvironment.