Tumor targeting and penetrating biomimetic mesoporous polydopamine nanoparticles facilitate photothermal killing and autophagy blocking for synergistic tumor ablation.

The synergistic manipulation of autophagy blocking with tumor targeting and penetration effects to enhance cancer cell killing during photothermal therapy (PTT) remains a substantial challenge. Herein, we fabricated a biomimetic nanoplatform by precisely coating homologous prostate cancer cell membranes (CMs) onto the surface of mesoporous polydopamine nanoparticles (mPDA NPs) encapsulating the autophagy inhibitor chloroquine (CQ) for synergistically manipulating PTT and autophagy for anticancer treatment. The resulting biomimetic mPDA@CMs NPs-CQ system could escape macrophage phagocytosis, overcome the vascular barrier, and home in the homologous prostate tumor xenograft with high tumor targeting and penetrating efficiency. The mPDA NPs core endowed the mPDA@CMs NPs-CQ with good photothermal capability to mediate PTT killing of prostate cancer cells, while NIR-triggered CQ release from the nanosystem further arrested PTT-induced protective autophagy of cancer cells, thus weakening the resistance of prostate cancer cells to PTT. This combined PTT killing and autophagy blocking anticancer strategy could induce significant autophagosome accumulation, ROS generation, mitochondrial damage, endoplasmic reticulum stress, and apoptotic signal transduction, which finally results in synergistic prostate tumor ablation in vivo. This prostate cancer biomimetic nanosystem with synergistically enhanced anticancer efficiency achieved by manipulating PTT killing and autophagy blocking is expected to serve as a more effective anticancer strategy against prostate cancer. STATEMENT OF SIGNIFICANCE: Autophagy is considered as one of the most efficient rescuer and reinforcement mechanisms of cancer cells against photothermal therapy (PTT)-induced cancer cell eradication. How to synergistically manipulate autophagy blocking with significant tumor targeting and penetration to enhance PTT-mediated cancer cell killing remains a substantial challenge. Herein, we fabricated a biomimetic nanoplatform by precisely coating homologous cancer cell membranes onto the surface of mesoporous polydopamine nanoparticles with encapsulation of the autophagy inhibitor chloroquine for synergistic antitumor treatment with high tumor targeting and penetrating efficiency both in vitro and in vivo. This biomimetic nanosystem with synergistically enhanced anticancer efficiency by manipulating PTT killing and autophagy blocking is expected to serve as a more effective anticancer strategy.