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

Abstract

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 granulocytemacrophage colony-stimulating factor and cytosine-phosphodiesterguanine-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.

Stimuli‐Responsive Nanocomposite Hydrogels for Biomedical Applications

“…Following a similar rationale, injectable alginate cryogels have been recently loaded with pH‐responsive acetalated dextran nanoparticles carrying Nutlin‐3a, a potent p53 activator for tumor suppression. [ 29 ] This was achieved by adding nanoparticle solutions on top of the hydrogels surface and allowing adsorption to take place along time. Unlike previous examples which were attempted on much thinner hydrogel films, confocal microscopy imaging of the thicker cryogel showed abundant accumulation of nanoparticles at the surface but limited penetration towards deeper hydrogel regions.…”

Colorectal cancer triple co-culture spheroid model to assess the biocompatibility and anticancer properties of polymeric nanoparticles

“…In this study, polymeric NPs of Sp-AcDEX were prepared by a water-in-oil-in-water double emulsion technique, as previously described by our group [31,65]. Table 3 is attributed to the use of a different batch of polymer to produce FITC NPs.…”

Polysaccharide-based nanomedicines for cancer immunotherapy: A review

“…These nanomedicines could also maturate DCs by increasing the expression of CD83 and CD86 on their surfaces, which would enhance their antigen presenting abilities, induce proliferation and activation of the down-stream immune cells like cytotoxic CD8 + T cells, promote the secretion of IL-1β and reduce the expression of IL-10. Based on these findings, acetalated dextran nanoparticles-loaded injectable alginate cryogel was also introduced as an in situ cancer vaccine [ 292 ]. This peritumoral injectable cancer vaccine was reported to demonstrate cytotoxicity towards tumor cells and induce immunogenic cell death, which potentially decreased cancer recurrence.…”