Acetalated Dextran Nanoparticles Loaded into an Injectable Alginate Cryogel for Combined Chemotherapy and Cancer Vaccination

摘要

Vaccination represents a promising strategy for cancer therapy due to its ability to efficiently eliminate tumors from the host body and prevent their recurrence. Nevertheless, the current vaccines are still lacking efficacy. Combination therapies, such as those integrating chemotherapy with immunotherapy, represent a powerful tool to potentially circumvent this drawback. Herein, injectable alginate cryogels loaded with granulocyte-macrophage colony-stimulating factor and cytosine-phosphodiester-guanine-rich oligonucleotides, are combined with spermine-modified acetalated dextran nanoparticles (Sp-AcDEX NPs), loaded with p53 activator Nutlin-3a (Nut-3a) for combined chemoimmunotherapy. The Sp-AcDEX NPs are successfully loaded into the alginate cryogels and released over time. Furthermore, the delivery of the NPs from the cryogel enhances their accumulation in tumor tissue following peritumoral injection. Nut-3a exerts toxicity towards the tumor cells and induces immunogenic cell death through the upregulation of surface calreticulin expression. Overall, this combination is a promising strategy to reduce cancer cell proliferation, induce immunogenic cell death, and accumulate drug payloads into the tumor. This approach may avoid cancer recurrence through the induction of in situ cancer vaccination mediated by antigens and danger signals released from the apoptotic cancer cells.