Manganese‐CpG Nanocomposite Integrates ROS‐Induced Cell Apoptosis and STING‐Activated and Adjuvant‐Augmented Immune Responses for Tumor Elimination and Prevention

Abstract

Chemodynamic therapy (CDT) based on Fenton‐like reaction possesses great potential for anticancer therapy with high efficiency and specificity. However, CDT still suffers low therapeutic efficiency due to intratumoral insufficient H2O2 or unfavorable tumor microenvironment. To enhance tumor treatment and in particular prevent tumor recurrence, the combined strategies with CDT are essentially needed. Herein, a nanocomposite based on Mn2+ and cytosine‐phosphate‐guanine oligonucleotides (CpG ODNs) (MnCpGPNCs) is constructed to combine CDT with immunostimulating responses by exploiting Mn2+‐induced CDT and Mn2+/CpG ODNs‐coinduced immunotherapy against mouse colon tumor cells. Specifically, MnCpGPNCs efficiently deliver and sensitively release Mn2+ in tumor cells to trigger Fenton‐like reaction, causing cell apoptosis. Importantly, Mn2+ also promotes the stimulator of interferon genes pathway to increase the production of type I interferons, thus increasing cytotoxic T lymphocyte infiltration, dendritic cell maturation, and proinflammatory cytokine secretion. Furthermore, CpG ODNs serve as immune adjuvant enhanced the antigen presentation and immune‐eliciting potency. The combination of Mn2+‐based CDT with augmented immunotherapy efficiently inhibits the primary/distance tumors and prevents tumorigenesis. Overall, this newly developed metal‐CpG system demonstrates a paradigm to expand chemodynamic agents as immunotherapy boosters to complement current treatments for tumor elimination and prevention.

Emerging nanoparticle platforms for CpG oligonucleotide delivery

“…130 More recently, Mn 2+ was also reported to promote the production of type I interferons, thus improving the infiltration of cytotoxic T lymphocytes, the maturation of dendritic cells, and the secretion of proinflammatory cytokines. 131 In addition to Mn-based nanocarriers, Lu's group reported on the design of chitosan-decorated hollow CuS NPs loaded with CpG motifs as an NIR-induced transformative nanoplatform. The laser could induce the breakdown of CuS NPs, improving the tumor retention.…”

“…130 More recently, Mn 2+ was also reported to promote the production of type I interferons, thus improving the infiltration of cytotoxic T lymphocytes, the maturation of dendritic cells, and the secretion of proinflammatory cytokines. 131…”