Journal
CARBOHYDRATE POLYMERS
Volume 289, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2022.119455
Keywords
Hyaluronan-cholesterol conjugate; Combination chemotherapy; Cancer stem cell (CSC) makers; Photodynamic therapy; SN38; Hyaluronan nanoparticles; Chemo-resistant ovarian cancer; Thioketal drug conjugate; CD44-targeting
Categories
Funding
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MOE and MSIT) [2020R1I1A1A01073559, 2020R1A2B5B02002377, 2018R1A6A1A03025523, 2019M3E5D1A02069623]
- Basic Science Research Program
- National Research Foundation of Korea [2020R1I1A1A01073559] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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.
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