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Nanoenabled Disruption of Multiple Barriers in Antigen Cross-Presentation of Dendritic Cells via Calcium Interference for Enhanced Chemo-Immunotherapy
journal contribution
posted on 2020-05-22, 14:09 authored by Jingyi An, Kaixiang Zhang, Binghua Wang, Sixuan Wu, Yifei Wang, Hongling Zhang, Zhenzhong Zhang, Junjie Liu, Jinjin ShiChemo-immunotherapy
holds the advantage of specific antitumor effects
by activating T cell immune response. However, the efficiency of chemo-immunotherapy
is restricted to the insufficient antigen presentation of dendritic
cells (DCs) in the tumor immunosuppression microenvironment. Here,
we rationally designed a simple yet versatile calcium ion nanogenerator
to disrupt the autophagy inhibition condition within DCs, enrich damage-associated
molecular patterns (DAMPs), and attenuate acidity in the tumor microenvironment.
After chemotherapy, honeycomb calcium carbonate (CaCO3)
nanoparticles (OVA@CaCO3, denoted as HOCN, ovalbumin (OVA)
acted as skeleton) could preferentially accumulate in the tumor and
display a series of benefits for disrupting multiple barriers in antigen
cross-presentation of DCs: (i) recovering cell viability of DCs by
HOCN-induced tumor acidity attenuating; (ii) disrupting the autophagy
inhibition condition in DCs by generating Ca2+ in cells;
(iii) improving maturation of DCs by Ca2+ overloading-mediated
enhanced DAMP release from tumor cells. In addition, HOCN can also
disrupt the immunosuppressive microenvironment by reducing the infiltration
of immunosuppressive cells and factors. We believe regulation of the
intratumoral Ca2+ offers an alternative strategy for improving
cancer chemo-immunotherapy.
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Keywords
antigen cross-presentationhoneycomb calcium carbonateOVAcancer chemo-immunotherapyalternative strategyHOCN-induced tumor acidity attenuatingtumor microenvironmentCalcium Interferencetumor cellsantitumor effectscalcium ion nanogeneratorautophagy inhibition conditionAntigen Cross-PresentationNanoenabled DisruptionDAMP releaseMultiple BarriersCaCO 3cell viabilityEnhanced Chemo-Immunotherapy Chemo-immunotherapyDCtumor immunosuppression microenvironmentantigen presentationattenuate aciditydendritic cellsT cellDendritic Cells
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