Manipulation of Mitophagy by "All-in-One" Nanosensitizer Augments Sonodynamic Glioma Therapy.

Manipulation of Mitophagy by "All-in-One" Nanosensitizer Augments Sonodynamic Glioma Therapy. Autophagy. 2019 Nov 01;: Authors: Qu F, Wang P, Zhang K, Shi Y, Li Y, Li C, Lu J, Liu Q, Wang X Abstract Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and non-invasive strategy for treating glioma. We innovatively designed a smart "all-in-one" nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the ...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research