The acidic microenvironment of tumors significantly reduces the anti-tumor effect of immunotherapy. Herein, a hierarchically structured fiber device is developed as a local drug delivery system for remodeling the acidic tumor microenvironment (TME) to improve the therapeutic effect of immunotherapy. Proton pump inhibitors in the fiber matrix can be sustainedly released to inhibit the efflux of intracellular H+ from tumor cells, resulting in the remodeling of the acidic TME. The targeted micelles and M1 macrophage membrane-coated nanoparticles in internal cavities of fiber can induce immunogenic cell death (ICD) of tumor cells and phenotypic transformation of tumor-associated macrophages (TAMs), respectively. The relief of the acidity in the TME further promotes ICD and the polarization of TAMs, alleviating the immunosuppressive microenvironment and synergistically enhancing the antitumor immune response. In vivo results reveal this local drug delivery system restores the pH value of TME from 6.8 to 7.2 and exhibit an excellent immunotherapeutic effect.
Keywords: acidic microenvironment; cancer immunotherapy; local drug delivery; nanocarriers; proton pumps.
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