Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress

Abstract

Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.

Cancer nanotechnology: current status and perspectives

“…One solution to amplify RT mediated oxidative stress to induce ICD for antitumor immunity activation was developed via a novel radiosensitizer that incorporates nanoscale coordination polymers (NCPs) based on Gd 3+ and 5′-Guanosine monophosphate (5′-GMP) via supramolecular self-assembly (Fig. 9 ) [ 347 ]. Hemin (PANHEMATIN®) with peroxidase-mimic catalytic activity was incorporated into the Gd 3+ /5′-GMP NCPs (Gd-NCPs) to form Hemin@ Gd 3+ /5′-GMP NCPs (H@Gd-NCPs).…”

“…Dendritic cells (DCs), glutathione (GSH), oxidized glutathione (GSSG), hydroxyl radicals (•OH), calreticulin (CRT), high mobility group protein B1 (HMGB1), adenosine triphosphate (ATP). Reprinted with permission, [ 347 ] 10.1038/s41467-020-20243-8 …”

Polymeric Nanosystems for Immunogenic Cell Death‐Based Cancer Immunotherapy

“…Reproduced with permission. [103] Copyright 2021, Springer Nature. moving trajectory of PEG CaCUR nanoparticles in vivo and their operational principle were completely presented in Figure 5a.…”

“…Huang and co‐workers designed a nanoscale coordination polymers (NCPs) composed of gadolinium (Gd 3+ ) and 5’‐Guanosine monophosphate through supramolecular self‐assembly, following by introducing peroxidase‐like Hemin into the nanosystem for endowing the polymers (Gd‐NCPs) with catalytic activity. [ 103 ] The presence of Gd, the H@Gd‐NCPs nanoparticles exhibited a promising magnetic resonance imaging (MRI) capacity even better than clinical MRI contrast agents. Moreover, Hemin loaded in H@Gd‐NCPs can act as peroxidase to deplete (glutathione) GSH via overexpressed H 2 O 2 in TME, which strengthen irradiation‐association oxidative stress and further trigger ICD.…”

“…f) Flow cytometry analysis of DCs maturation in tumor-draining lymph nodes, the TDLNs were harvested five days after RT. Reproduced with permission [103]. Copyright 2021, Springer Nature.…”