Journal
NANO LETTERS
Volume 20, Issue 9, Pages 6272-6280Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c01415
Keywords
chemoimmunotherapy; immunogenic cell death; dendritic cells recruitment; prostaglandin E-2
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Funding
- National Natural Science Foundation of China [81673021, U1804183, 81901878]
- China Postdoctoral Science Foundation [2019M662553]
- Key Scientific Research Project (Education Department of Henan Province) [20HASTIT049]
- Key Scientific Research Projects Plan of Henan Higher Education Institutions [20A350011]
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Although immunogenic cell death (ICD)-based chemoimmunotherapy elicits an immune response, it always focuses on eliminating seeds (tumor cells) but neglects soil (tumor microenvironment, TME), leading to tumor growth and metastasis. Herein, a type of detachable coreshell nanoplatform (DOX@HA-MMP-2-DEAP/CXB) is developed, which could swell in the acidic TME because of the protonation of the 3-diethylaminopropyl isothiocyanate (DEAP) inner core for celecoxib (CXB) release, while hyaluronic acid@doxorubicine (HA@DOX) prodrug in the outer shell could release by the cleavage of matrix metalloproteinase-2 (MMP-2) peptide. HA@DOX targets tumor cells precisely for triggering ICD. And CXB acts on multiple immune cells to remodulate TME, such as increasing the infiltration of dendritic cells (DCs) and T cells, decreasing the infiltration of the immunosuppressive cells, and eliminating the physical barriers between T cells and tumor cells. For comparison, HA-DOCA/DOX/CXB traditional nanoparticles are constructed. And DOX@HA-MMP-2-DEAP/CXB performs an impressive antitumor effect, which shows potential in enhancing the effect of chemoimmunotherapy.
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