CD44-Specific Targeting Nanoreactors with Glutathione Depletion for Magnifying Photodynamic Tumor Eradication

Photodynamic therapy ( PDT) is an efficacious noninvasive therapeutic modality that utilizes nontoxic photosensitizers (PSs) to transform oxygen into highly cytotoxic reactive oxygen species (ROS) under specific light irradiation. However, low intratumoral accumulation capacity and the reduced ROS production caused by excessive glutathione (GSH, a scavenger of ROS) in the tumor microenvironment (TME) immensely limit PDT therapeutic efficacy. Hence, an innovative nanoreactor AM-L@NBS was constructed using DSPE-PEG2k-Maleimide and CD44-specific polypeptide (A6) modified liposome to encapsulate sulfur substituted Nile blue (NBS). NBS, as a near-infrared (NIR) PS, possesses not only a simple synthesis but also an extremely low IC50 (0.024 mu M) compared with commercial Ce6 (5.16 mu M) at a tiny light-dose irradiation of 6 J/cm(2) in MCF7 cells. Encouragingly, AM-L@NBS revealed significantly increased uptake and retention in breast cancer with CD44 overexpression. Furthermore, AM-L@NBS can exhaust the intracellular GSH and upregulate ROS levels, causing explosive apoptosis to cancer cells. In brief, the abundant enrichment of nanomedicine and augmented ROS could amplify the PDT efficacy to achieve tumor ablation; the prepared nanoreactor possesses excellent biocompatibility and provides a novel clinical strategy. [GRAPHICS] .