Affiliation:
1. Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Suzhou Medical College of Soochow University Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
Abstract
AbstractT cell dysfunction‐induced tumor immune escape is particularly severe in glioblastoma (GBM), and significantly affects the efficacy of immunotherapy. It is crucial to innovatively reverse the T cell dysfunction for improving GBM immunotherapy. Herein, T cell dysfunction is remarkably reversed and immunotherapy of GBM is boosted by repurposing the U. S. Food and Drug Administration‐approved antidepressant paroxetine (PX) with biomimetic nanoparticles (CS‐J@CM/6 NPs). The PX is successfully applied to abrogate T cell sequestration in the bone marrow of GBM‐bearing mice and increase their infiltration in tumor. The biomimetic NPs are composed of ultrasmall Cu2−xSe NPs, JQ1, and tumor cell membrane modified with CD6, and are efficiently delivered into tumor through the specific interactions between CD6 and activated leukocyte cell adhesion molecule. They ameliorate the T cell dysfunction through the double roles of loaded JQ1, which simultaneously decreases the expression of PD‐1 and TIM‐3 on T cells, and the expression of PD‐L1 on tumor cells. The NP also induces the immunogenic cell death of tumor cells to activate immune response. The synergistic roles of PX and biomimetic CS‐J@CM/6 NPs notably enhance the survival of GBM‐bearing mice. This work provides new insights into tumor immunotherapy by repurposing “old drugs” with advanced NPs.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions
China Postdoctoral Science Foundation
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
5 articles.
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