Novel Carrier-Free
Nanodrug Enhances Photodynamic
Effects by Blocking the Autophagy Pathway and Synergistically Triggers
Immunogenic Cell Death for the Efficient Treatment of Breast Cancer
Photosensitizers have been widely used to cause intratumoral
generation
of reactive oxygen species (ROS) for cancer therapy, but they are
easily disturbed by the autophagy pathway, a self-protective mechanism
by mitigating oxidative damage. Hereby, we reported a simple and effective
strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based
on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the
autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided
the unexpected toxicity caused by the regular nanocarrier and also
ameliorated its stability in different conditions. Light-activated
Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell
death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered
self-healing in tumor cells and enhanced photodynamic therapy (PDT)
to exert a more potent killing effect and more efficient ICD. Also,
Ce6@CQ could effectively accumulate in the xenograft breast tumor
site in a mouse model through the enhanced permeability and retention
(EPR) effect, and the growth of breast tumors was effectively inhibited
by Ce6@CQ with light. Such a carrier-free nanodrug provided a new
strategy to improve the efficacy of PDT via the suppression of autophagy
to digest ROS-induced toxic substances.