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Advanced materials: biomimetic mineralized bacterial outer membrane vesicles for safe and efficient improvement of tumor microenvironment and tumor therapy

wallpapers News 2020-09-06

tumor immunotherapy can kill tumor cells by activating human autoimmune function which has a very broad application prospect. However tumor immunosuppressive microenvironment has become a key problem limiting the effectiveness of tumor immunotherapy. It is a classic strategy to enhance the immune efficacy of tumor by using synthetic particles to deliver drugs that regulate tumor microenvironment to tumor sites. However in the preparation process of synthetic particle carrier not only chemical coupling drug embedding other steps need to be introduced but also the hydrophilicity surface charge molecular weight other factors between particle carrier drug molecules need to be fully considered. Therefore it is still very challenging significant to find a simple safe efficient particle carrier.

researchers Ma Guanghui Wei Wei from the Institute of process engineering Chinese Academy of Sciences have discovered the great potential of bacterial outer membrane vesicles in regulating tumor microenvironment proposed that they can be used as tumor immunotherapy system to achieve safe efficient regulation of tumor immune microenvironment without complicated preparation process artificial addition of immunostimulatory drugs. The team first screened omve. Coli (BL21) which has the strongest ability to improve tumor microenvironment from different sources of OMVs then constructed a tumor immunotherapy system. In order to avoid the toxic side effects of cytokine storm antibody specific clearance caused by direct intravenous injection of OMVs a bio safe calcium phosphate "invisible shell" was grown on the surface of exposed OMVs by biomimetic mineralization so as to shield the risk signals antibody recognition sites of OMVs increase the safety of the system prolong the internal circulation time. When the mineralized particles reach the tumor with the help of nanoparticles the acid environment of the tumor makes the calcium phosphate shell dissolve. The exposed OMVs can effectively improve the microenvironment of tumor immunosuppression by promoting the infiltration of cytotoxic T cells the polarization of M2 macrophages to M1 macrophages. At the same time the dissolution of calcium phosphate shell neutralizes the H in the microenvironment the improvement of acid microenvironment can further promote the growth of tumor cells The macrophages of M2 type were polarized to M1 type. These synergistic effects can reverse the tumor immunosuppressive microenvironment enhance the killing function of immune cells effectively inhibit the growth of tumor. In addition the biomimetic mineralization strategy can also achieve the organic combination of multiple functional molecules mineralized particles which can be used to prepare mineralized particles with tumor targeting lig folate photosensitizer indocyanine green The mineralized particles of ICG can achieve the active targeting function of the treatment system or photothermal immunotherapy so as to further improve the therapeutic effect of malignant tumor.

immunotherapy system based on nanoparticles have made important contributions to the development of new dosage forms for immunotherapy. Researchers Ma Guanghui Wei Wei from the biological dosage forms biomaterials team of the State Key Laboratory of biochemical engineering Institute of process engineering have carried out a series of in-depth studies on nanoparticles discovered created a series of new dosage forms of nanoparticles which have been successfully used in tumor treatment Some dosage forms have been approved by ethics to enter preclinical clinical research related work has been published in NAT mate 2018 17 187 NAT Biomed eng (DOI: 10.1038 / s41551-020-00624-6) NAT commun 2017 8 14537 SCI adv 2020 6 eaay7735 ADV mate 2018 31 1801067 ADV SCI 2017 4 1700083 ACS center SCI 2019 5 796 other journals.

this work has been supported by the group project of NSFC the national key R & D program the special project of strategic leading science technology of Chinese Academy of Sciences.


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