Pheophorbide A and SN38 conjugated hyaluronan nanoparticles for photodynamic- and cascadic chemotherapy of cancer stem-like ovarian cancer

In this study, we designed photo-triggered reactive oxygen species (ROS)-generating pheophorbide A and ROScleavable thioketal-SN38 conjugated hyaluronan-cholesterol nanoparticles (PheoA-SN38-HC NPs). And we observed the combined therapeutic effects of PheoA-SN38-HC NPs against HEY-T30 human ovarian cancer (OC) model. Clinical Proteomic Tumor Analysis Consortium (CPTAC) data showed that the expression of cancer stem cell (CSC) markers (CD44, ALDH1A1, and CD117) is highly associated with poor clinical outcomes in OC patients. We proved that HEY-T30 cells overexpress CSC markers and much more invasive than other cancer cells. Flow cytometry (FACS) and microscopic analysis revealed the active targeting property of PheoA-SN38-HC NPs to CD44+ HEY-T30 cells. Moreover, the combination therapeutic effect of PheoA-SN38-HC NPs was clearly demonstrated against in vitro HEY-T30 cells and an in vivo xenograft mouse model. In particular, the paracrine cytotoxic effect of SN38 probably compensates the locoregional therapeutic limitation of photodynamic therapy.

Automated summary

In this study, we designed a photo-triggered reactive oxygen species (ROS)-generating nanoparticle and demonstrated its combined therapeutic effects against ovarian cancer. The study also identified a correlation between cancer stem cell markers and poor clinical outcomes in ovarian cancer patients, and showed that the nanoparticle could actively target these cancer stem cells. The experimental results indicated therapeutic effects of the nanoparticle both in vitro and in vivo, potentially overcoming the local therapeutic limitation of photodynamic therapy.