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Detachable Nanoparticle-Enhanced Chemoimmunotherapy Based on Precise Killing of Tumor Seeds and Normalizing the Growing Soil Strategy
journal contribution
posted on 2020-08-06, 22:10 authored by Lei Wang, Kaili Ding, Cuixia Zheng, Huifang Xiao, Xinxin Liu, Lingling Sun, Rida Omer, Qianhua Feng, Zhenzhong ZhangAlthough
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
core–shell 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.