Application Of DSPE-PGEA Drug-loaded Nanomicelle System In Solid Tumor Immune Tolerance

As the world's most threatening disease to human life,the treatment of cancer has always been the focus of researchers.However,traditional treatment options have many drawbacks due to their toxic side effects and difficulties in suppressing metastatic tumors.Thanks to the development of nanotechnology,a variety of models of combined treatment of"cocktail" treatment programs have emerged.Immunotherapy has become one of the most promising methods for eliminating tumors using its own body reactions.However,the clinical immune response has only a good effect on some patients,which is a manifestation of immune tolerance.In order to reverse the immune tolerance and achieve excellent therapeutic effects,we believe that regulating the immune microenvironment is the most fundamental way.In this paper,we synthesized the hydrophilic cationic polymer PGMA by ATRP method,and opened it with hydrophobic DSPE to obtain self-assemblable amphiphilic polymer DSPE-PGEA.After the anti-cancer drug DOX was wrapped therein,a DSPE-PGEA drug-loaded nanomicelle system was obtained.Through a series of verifications,it is proved that the drug-loaded nanomicelle system has good encapsulation efficiency,drug loading and stability,and can be used for effective drug delivery and enrichment at the lesion site.In Chapter 3,we validated the reversal of immune tolerance in this nanomicelle system,which is achieved by the effective presentation of antigens.DOX causes tumor cells to undergo immunogenic cell death to release antigen,and the material adsorbs the antigen to effectively present it to APC cells,and activates T cells to kill tumors by autoimmunity.Through a series of in vivo experiments,we have demonstrated that by increasing the effective presentation of antigens,we have improved the immune microenvironment that tolerates tumors from a regulated form to a killing immune microenvironment,thereby killing tumors.In the later period,we also confirmed that this material can effectively prevent tumor recurrence and provide new ideas for immunotherapy.In summary,the DSPE-PGEA drug-loaded nanomicelle system was prepared and the immune microenvironment was improved by increasing the effective presentation of antigen.It has a good anti-tumor effect and prevents its recurrence,providing a new solution to overcome immune tolerance.