Construction\nof a Multifunctional Upconversion Nanoplatform\nBased on Autophagy Inhibition and Photodynamic Therapy Combined with\nChemotherapy for Antitumor Therapy

Inhibition of autophagy increases the sensitivity of\ntumor cells\nto radiotherapy and chemotherapy and improves the therapeutic effect\non tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy\nhas been proven to further improve the efficiency of cancer treatment.\nAs such, combining autophagy inhibition with PDT and chemotherapy\nmay represent a potentially effective new strategy for cancer treatment.\nHowever, currently widely studied autophagy inhibitors inevitably\nproduce various toxic side effects due to their inherent pharmacological\nactivity. To overcome this constraint, in this study, we designed\nan ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA\n+ NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN),\nCe6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA\n(MUCE) groups were set up separately as controls. Based on a combination\nof autophagy inhibition and PDT, the average particle size of MUCEN\nwas 197 nm, which can simultaneously achieve the double encapsulation\nof chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed\nthat MUCE was efficiently endocytosed by 4T1 cells under near-infrared\nlight irradiation. Further, in vivo tests revealed that MUCE dramatically\ninhibited tumor growth. Immunohistochemistry results indicated that\nMUCE efficiently increased the expression of autophagy inhibitors\np62 and LC3 in tumor tissues. The synergistic effect of autophagy\ninhibition and PDT with MUCE exhibited superior tumor suppression,\nproviding an innovative approach to cancer treatment.