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Tumor immunotherapy can kill tumor cells by activating the body's autoimmune function, which has the application prospect, but the micro-environment of tumor immunosuppression has become an important problem for the effectiveness of tumor immunotherapy.
Recently, a research team led by Ma Guangguang and Wei Wei, researchers at the Institute of Process Engineering of the Chinese Academy of Sciences, discovered the potential of simple bacterial outer membrane vesicles (OMVs) naturally secreted by bacteria in regulating the micro-environment of tumor immunosuppression, and adopted bionic mineralization strategies to make OMVs surfaces grow "invisible" calcium phosphate shells to avoid toxic side effects caused by simple OMVs intravenous injections.
, the effects of tumor therapy have been shown in mice.
, the system can also integrate target ligations, photosensitive agents and other functional molecules to enhance the treatment of malignant tumors.
the study was published on Advanced Materials.
The use of nanoparticles to deliver immunologic drugs to tumor sites is one of the strategies to improve the micro-environment of tumor immunosuppression, however, the immunotherapy system developed based on synthetic particles has difficult problems such as complicated preparation process, low drug loading rate and poor repetition between batches.
this end, the research team proposed the use of OMVs nanoparticles as a platform for cancer immunotherapy, without the need to artificially add immunostational stimulation drugs, can achieve safe and efficient tumor immuno-micro-environmental regulation.
researchers screened OMVE.coli (BL21) from different sources of OMVs to build a cancer immunotherapy system.
In order to avoid the toxic side effects such as cytokine storms and antibody-specific removal caused by simple OMV direct intravenous injection, through bionic mineralization, the exposed OMVs surface grows a bio-safe calcium phosphate "stealth shell", thereby shielding OMVs from warning signals and antibody identification sites, increasing the safety of the system and prolonging its in vivo circulation time.
When mineralized particles reach the tumor with nanoparticle size, the micro-acid environment at the tumor site causes the calcium phosphate shell to dissolve, and the exposed OMVs improve the microenta of tumor immunosuppression by promoting the immersion of cytotoxic T-cells and the polarization of M2 macrophages to M1;
these synergies to disrupt the tumor immunosuppression micro-environment, enhance the killing function of immune cells, can effectively inhibit the growth of tumors.
In addition, the bionic mineralization strategy can also achieve a variety of functional molecules and mineralized particles of organic combination, in order to prepare the addition of tumor-targeted ligand folic acid mineralized particles, as well as the addition of photosensitive agent indocyanine green (ICG) mineralized particles, can achieve the active targeting function of the treatment system or photothermal immunotherapy, improve the treatment of malignant tumors.
The contribution of nanoparticle-based immunotherapy systems to the development of new dosage forms for immunotherapy, researchers have studied nanoparticles and found and created a series of nanoparticle new dosage forms for immunological prevention and treatment of major diseases or infectious diseases such as tumors, hepatitis B and influenza, some of which have been ethically approved for preclinical and clinical studies, the results of which were published in Nat Mater 2018, 17, 187; Nat Biomed Eng; Nat Commun 2017, 8, 14537; Sci Adv 2020, 6, eaay7735; Adv Mater 2018, 31, 1801067; Adv Sci 2017, 4, 1700083; ACS Cent Sci 2019, 5, 796, etc.
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