biostudies-literatureYang LNatural Science Foundation of Anhui Provincethe National Key Research and Development ProgramNatural Science Foundation of Shanghaithe National Natural Science Foundation of China328https://www.ebi.ac.uk/biostudies/studies/S-EPMC8524820biostudies-literatureUnknown19(1)The tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8⁺ T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.Journal of nanobiotechnologyMultifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy.PMC85248202108085QC1073207140121ZR14663002016YFA010080031727801820731723177092320ZR1461600Qian YYang LWang SLi FCao YNiu JLiu QSun FLi AJing GfalseMultifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy.The tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8⁺ T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.2021-01-01T00:00:00Z2021 Oct2025-04-18T15:41:35.372Z2025-02-19T00:18:26.956ZS-EPMC85248203466335410.1186/s12951-021-01073-2