CD133 peptide-conjugated pyropheophorbide-a as a novel photosensitizer for targeted photodynamic therapy in colorectal cancer stem cells. (13th January 2021)

• Record Type: Journal Article
• Authors: Yan, Shichao; Tang, Da; Hong, Zhangyong; Wang, Jing; Yao, Hui; Lu, Lu; Yi, Huimei; Fu, Shujun; Zheng, Chanjuan; He, Guangchun; Zou, Heng; Hou, Xuyang; He, Qing; Xiong, Li; Li, Qinglong; Deng, Xiyun
• Is Part Of: Biomaterials science. Volume 9:Number 6(2021)
• Page Start: 2020
• Page End: 2031
• Publication Date: 2021-01-13
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d0bm01874k
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Colorectal cancer (CRC) is the third most common cancer around the world. Abstract : Colorectal cancer (CRC) is the third most common cancer around the world. Recent findings suggest that cancer stem cells (CSCs) play a pivotal role in the resistance to current therapeutic modalities, including surgery and chemotherapy. Photodynamic therapy (PDT) is a promising non-invasive therapeutic strategy for advanced metastatic CRC. Traditional photosensitizers such as pyropheophorbide-a (Pyro) lack tumor selectivity, causing unwanted treatment-related toxicity to the surrounding normal tissue. In order to enhance the targeting properties of Pyro, we synthesize a novel photosensitizer, CD133–Pyro, via the conjugation of Pyro to a peptide domain targeting CD133, which is highly expressed on CRC CSCs and correlated with poor prognosis of CRC patients. We demonstrate that CD133–Pyro possesses the targeted delivery capacity both in CRC CSCs derived from HT29 and SW620 cell lines and in a xenograft mouse model of tumor growth. CD133–Pyro PDT can promote the production of reactive oxygen species (ROS), suppress the stemness properties, and induce autophagic cell death in CRC CSCs. Furthermore, CD133–Pyro PDT has a potent inhibitory effect on CRC CSC-derived xenograft tumors in nude mice. These findings may offer a useful and important strategy for the treatment of CRC through targeting CSCs.