Abstract
Hypericin (HYP) is an effective photosensitizer for photodynamic therapy (PDT). However, it has not been widely applied in clinical studies because of its low water solubility. In this study, hyaluronic acid-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (HA-DSPE-PEG2000) and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) were used to produce mixed micelles for the delivery of HYP (HA/HYP MM). The targeting ligand HA was conjugated to DSPE-PEG2000 as a novel biomaterial for the targeted drug delivery of HYP. The optimized HA/HYP MM exhibited excellent stability, biosecurity, and sustained drug release. Compared with free HYP and HYP MM, HA/HYP MM showed a stronger inhibitory effect against MCF-7 and MDA-MB-231 cells. No obvious toxicity was observed in normal breast cells. A cellular uptake study confirmed that HA could significantly increase intracellular HYP accumulation in tumor cells via the CD44 receptor. Further mechanistic studies showed that HA/HYP MM increased the intracellular reactive oxygen species (ROS) levels and induced cell death. HA/HYP MM may be an effective drug delivery system for breast cancer photodynamic therapy.
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