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Article Abstract
Immunosuppressive microenvironment and poor immunogenicity are two stumbling blocks in anti-tumor immune activation. Tumor associated macrophages (TAMs) play crucial roles in immunosuppressive microenvironment, while immunogenic cell death (ICD) is a typical strategy to boost immunogenicity. Herein, we developed a coordinative modular assembly-based self-reinforced nanoparticle, (CaO/TA)-(Fe/BSA) which integrated CaO, Fe-tannic acid coordinated networks and albumin under the instruction of molecular dynamics simulation. (CaO/TA)-(Fe/BSA) could significantly enhance Fenton reaction through Fe self-reduction and HO self-sufficiency, and simultaneously increased intracellular accumulation of Ca. The self-augmented Fenton reaction with sufficient reactive oxygen species effectively repolarized TAMs and elicited ICD with Ca overload. Besides, (CaO/TA)-(Fe/BSA) was confirmed to self-reinforce deep tumor drug delivery by "treatment-delivery" positive feedback based on gp60-mediated transcytosis and M2-like macrophages repolarization-mediated perfusion promotion. Resultantly, (CaO/TA)-(Fe/BSA) effectively alleviated immunosuppression, provoked local and systemic immune response and potentiated anti-PD-1 antibody therapy. Our strategy highlights a facile and controllable approach to construct penetrated effective antitumor nano-immunotherapeutic agent.
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| http://dx.doi.org/10.1016/j.jconrel.2024.06.020 | DOI Listing |
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