2. Academic Validation
  3. Smart glypican-3-targeting peptide-chlorin e6 conjugates for targeted photodynamic therapy of hepatocellular carcinoma

Smart glypican-3-targeting peptide-chlorin e6 conjugates for targeted photodynamic therapy of hepatocellular carcinoma

  • Eur J Med Chem. 2024 Jan 15:264:116047. doi: 10.1016/j.ejmech.2023.116047.
Yuxin Fang 1,  Haoqian Ma 1,  Xianghua Zhang 2,  Peifeng Zhang 3,  Yu Li 1,  Shipeng He 4,  Chunquan Sheng 5,  Guoqiang Dong 6
Affiliations

Affiliations

  • 1 The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai, 200433, China.
  • 2 The Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200003, China.
  • 3 The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai, 200433, China; National & Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of Biomass, School of Pharmacy, Changzhou University, Changzhou, 213164, China.
  • 4 Institute of Translational Medicine, Shanghai University, 99 Shangda Road, Shanghai, 200444, China. Electronic address: [email protected].
  • 5 The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai, 200433, China. Electronic address: [email protected].
  • 6 The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai, 200433, China. Electronic address: [email protected].
PMID: 38118394 DOI: 10.1016/j.ejmech.2023.116047
Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive and lethal malignancy with poor prognosis, necessitating the urgent development of effective treatments. Targeted photodynamic therapy (PDT) offers a promising way to selectively eradicate tumor cells without affecting normal cells. Inspired by promising features of peptide-drug conjugates (PDCs) in targeted Cancer therapy, herein a novel glypican-3 (GPC3)-targeting PDC-PDT strategy was developed for the precise PDT treatment of HCC. The GPC3-targeting Photosensitizer conjugates were developed by attaching GPC3-targeting peptides to chlorin e6. Conjugate 8b demonstrated the ability to penetrate HCC cells via GPC3-mediated entry process, exhibiting remarkable tumor-targeting capacity, superior antitumor efficacy, and minimal toxicity towards normal cells. Notably, conjugate 8b achieved complete tumor elimination upon light illumination in a HepG2 xenograft model without harm to normal tissues. Overall, this innovative GPC3-targeting conjugation strategy demonstrates considerable promise for clinical applications for the treatment of HCC.

Keywords

Cancer treatment; Chlorin e6; Glypican-3; Hepatocellular carcinoma; Peptide-drug conjugates; Targeted photodynamic therapy.

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