Programmed Catalytic Therapy and Antigen Capture‐Mediated Dendritic Cells Harnessing Cancer Immunotherapies by In Situ‐Forming Adhesive Nanoreservoirs

Abstract

T lymphocyte recruitment and infiltration promises to suppress the most devastating metastatic tumors for immunotherapy. However, the immune privilege and low vaccine immunogenicity usually reduces the presence of lymphocytes in tumors, especially for invading metastatic clusters. Here, an adhesive catalytic nanoreservoir (CN) containing manganese dioxide (MnO2) and catechol‐functionalized magnetic metal organic framework for the antigens capture and delivery is reported. The intravenously injected CN accumulates at tumor via the marginated target and in situ forming gel for antigen capture. At tumor site, CN releases Mn2+ for redox reactions by depleting glutathione (GSH) and Fenton‐like activity, i.e., chemodynamic therapy (CDT). Accompanying with hyperthermia, CDT promote the tumor to release the tumor‐associated antigens including neoantigens and damage‐associated molecular patterns. Then, the gels with catechol groups act as antigen reservoirs and deliver the autologous tumor‐associated antigens to dendritic cells, achieving sustained immune stimulation. The in situ‐forming catalytic nanoreservoir at lung metastasis as a magnetothermal‐induced antigen reservoir effectively inhibited the tumor in 60 days and increased the survival rate.

Nanocatalysts for modulating antitumor immunity: fabrication, mechanisms and applications

“…12A). 441 At the tumor site, ˙OH can be released through Fenton-like reaction for the consumption of intracellular GSH to induce the immunogenic death. The released tumor antigens were captured by the catechol nanogels for antigen presentation to achieve continuous immune stimulation.…”

“…The released tumor antigens were captured by the catechol nanogels for antigen presentation to achieve continuous immune stimulation. 441 In addition to releasing tumor antigens, Fenton nanocatalysts have been applied to activate the stimulator of interferon genes (STING) pathway of tumors for immune activation (Fig. 12B and C).…”

Advancing nanotechnology for neoantigen-based cancer theranostics

“…Then, the HSR causes a range of speedy alterations in gene expression patterns; for example, the production of HSPs will alleviate the effects of the heat damage. 111 Similar to PDT, PTT also can induce ICD to promote tumour cell apoptosis and release tumour endogenous neoantigens, 71,95,119,122,123 which further boosts the immune responses and obviously inhibits tumour proliferation, metastasis, and recurrence. 97 Thus, we will discuss exo/endogenous neoantigen-based PTT in this section.…”

Metal–organic gels: recent advances in their classification, characterization, and application in the pharmaceutical field

“…MOGs, combining the porous qualities of rigid MOFs with the self-healing and injectable properties of soft hydrogels, exhibit sustained/controlled drug release, enhanced drug stability, and promoted drug absorption properties. These favorable properties make them appropriate for development as injections and implants to realize drug delivery, 15,123,162,190 as well as tissue repair and regeneration. 141,171,182,183 For instance, an injectable MOG cross-linked by a dynamic coordination bond between the bisphosphonate group and Zn 2+ ion was designed, which served as a local release platform for the chemotherapeutic drugs 5-fluorouracil and doxorubicin.…”

“…207 MOGs are effective vehicles for the persistent delivery of tumor-associated antigens. 15 Yalamandala et al 190 designed an injectable adhesive catalytic nano reservoir, which was composed of poly(N-isopropylacrylamide)/ polydopamine hybrid nanogel, catechol-functionalized magnetic MOF, and manganese dioxide. This MOG released Mn 2+ through marginal target aggregation at the tumor sites, then caused the apoptosis of cancer cells and the release of tumorassociated antigens.…”