Although
the strategies to induce dendritic cells (DCs) maturation
and promote their antigen presentation can stimulate the tumor immune
response, the endogenous deficiency and immunosuppression of DCs reduce
antigen utilization, which limits antigen presentation efficiency
and reduces immunotherapy effectiveness. Here, we report an endogenous
stimulus-responsive nanodelivery system (DOX@HFn-MSO@PGZL). On the
one hand, doxorubicin (DOX) promoted antigen presentation by DCs after
the immunogenic death of tumor cells. On the other hand, l-methionine sulfoximine (MSO) regulated the glutamine metabolism
of tumor-associated macrophages (TAMs) to induce a shift toward the
M1-type. M1-TAMs synergistically presented antigens with mature DCs
and were more frequently produced to destroy the tumor suppressive
immune microenvironment, resulting in the alleviation of DCs functional
inhibition. Ultimately, the antigen presentation efficiency was improved,
completely activating tumor immunity and exhibiting powerful antitumor
effects.
Multidrug resistance is still a major obstacle to cancer treatment. The most studies are to inhibit the activity of the drug transporter P-glycoprotein (P-gp), but the effect is not ideal. Herein, a nanosystem was built based on cascade catalytic consumption of cholesterol. Cholesterol oxidase (natural enzyme, COD) was immobilized on the carrier (NH2-MIL-88B, MOF) through amide reaction, COD catalyzed the consumption of cholesterol, the reaction product H2O2 was further produced by the MOF with its peroxidase-like activity to produce hydroxyl radicals (•OH) with killing effect. Due to the high expression of CD44 receptor on the surface of tumor cells, we encapsulated chondroitin sulfate gel shell (CS-shell) with CD44 targeting and apoptosis promoting effect on the surface of DOX@MOF-COD nanoparticles, which can accurately and efficiently deliver the drugs to the tumor site and improve the effect of reversing drug resistance. Taking drug-resistant cell membrane as "breakthrough", this paper will provide a new idea for reversing multidrug resistance of tumor.
Graphical Abstract
In tumor immunotherapy, Treg cells are immunosuppressive cells. Generally, the main strategies of chemo immune-therapy for Treg cells are to eliminate them by using chemotherapy drugs combined with immune checkpoint...
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