Biomimetic MOF‐Based Nano‐Immunoactivator via Disruption of Ion Homeostasis for Strengthened Tumor Microwave‐Immunotherapy

Author:

Chen Zengzhen12,Guo Wenna123,Tan Longfei12,Fu Changhui12,Wu Qiong12,Ren Xiangling12,Jiang Guihua4,Ma Tengchuang5,Meng Xianwei12ORCID

Affiliation:

1. State Key Laboratory of Cryogenic Science and Technology Technical Institute of Physics and Chemistry Chinese Academy of Sciences Beijing 100190 China

2. Guangdong Second Provincial General Hospital Jinan University Guangzhou 510315 China

3. Laboratory of Controllable Preparation and Application of Nanomaterials Technical Institute of Physics and Chemistry Chinese Academy of Sciences Beijing 100190 China

4. School of Optoelectronic Science and Engineering University of Electronic Science and Technology of China Chengdu 610054 China

5. Department of Nuclear Medicine Harbin Medical University Cancer Hospital Harbin 150086 China

Abstract

AbstractImmunogenic cell death (ICD) is a promising strategy for anticancer immunity by inducing antigen‐presenting cell maturation. However, the traditional ICD inducers, such as chemotherapeutic agents, have largely hampered their application by severe side effects and low tumor selectivity. The changes intra/extracellular ion concentrations affect the growth and metastasis of tumor cells. Interference with ion homeostasis can induce tumor cell death and elicit immune responses. Here, a biomimetic Ga‐based metal–organic framework (MOF) coated with red blood cell–platelet fusion membrane (RPM), that is, 5‐fluorouracil@GaMOF@RPM (5‐FUGR) nano‐immunoactivator, is reported as a highly efficient ICD inducer for enhanced microwave (MW)‐immunotherapy. Following intravenous administration, 5‐FUGR accumulates to tumor site via RPM biomimetic modification‐mediated long circulation and active targeting. The structure of 5‐FUGR undergoes degradation and releases Ga3+. MW combined with high concentrations of Ga3+ disrupts intracellular ion homeostasis, which leads to severe oxidative stress and intracellular Ca2+ retention to promote apoptosis of tumor cells. More importantly, 5‐FUGR combined with MW not only completely eradicates 4T1 primary tumors, but also induces efficient ICD, immune initiation, and memory effects to inhibit metastatic and recurrence of the tumor. Thus, 5‐FUGR, as a strong ICD inducer, provides new insights into achieving tumor immunity in combination with other therapies.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Beijing Municipality

China Postdoctoral Science Foundation

Natural Science Foundation of Heilongjiang Province

Publisher

Wiley

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