Inhibition of autophagy increases the sensitivity of
tumor cells
to radiotherapy and chemotherapy and improves the therapeutic effect
on tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy
has been proven to further improve the efficiency of cancer treatment.
As such, combining autophagy inhibition with PDT and chemotherapy
may represent a potentially effective new strategy for cancer treatment.
However, currently widely studied autophagy inhibitors inevitably
produce various toxic side effects due to their inherent pharmacological
activity. To overcome this constraint, in this study, we designed
an ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA
+ NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN),
Ce6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA
(MUCE) groups were set up separately as controls. Based on a combination
of autophagy inhibition and PDT, the average particle size of MUCEN
was 197 nm, which can simultaneously achieve the double encapsulation
of chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed
that MUCE was efficiently endocytosed by 4T1 cells under near-infrared
light irradiation. Further, in vivo tests revealed that MUCE dramatically
inhibited tumor growth. Immunohistochemistry results indicated that
MUCE efficiently increased the expression of autophagy inhibitors
p62 and LC3 in tumor tissues. The synergistic effect of autophagy
inhibition and PDT with MUCE exhibited superior tumor suppression,
providing an innovative approach to cancer treatment.