CD133 peptide-conjugated pyropheophorbide-a as a novel photosensitizer for targeted photodynamic therapy in colorectal cancer stem cells
| Autor: | Shichao Yan, Lu Lu, Xuyang Hou, Da Tang, Hui Yao, Li Xiong, Huimei Yi, Shujun Fu, Zhangyong Hong, Heng Zou, Guangchun He, Xiyun Deng, Qing He, Jing Wang, Qinglong Li, Chanjuan Zheng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Colorectal cancer
medicine.medical_treatment Biomedical Engineering Mice Nude Photodynamic therapy Mice 03 medical and health sciences 0302 clinical medicine Cancer stem cell Cell Line Tumor medicine Animals Humans General Materials Science Photosensitizer neoplasms 030304 developmental biology 0303 health sciences Chemotherapy Photosensitizing Agents business.industry Autophagy Cancer medicine.disease digestive system diseases Photochemotherapy 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research Stem cell Colorectal Neoplasms Peptides business |
| Zdroj: | Biomaterials Science. 9:2020-2031 |
| ISSN: | 2047-4849 2047-4830 |
| DOI: | 10.1039/d0bm01874k |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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