TY - JOUR
T1 - Development a novel drug delivery formulation targeting to esophageal squamous cell carcinoma
AU - Feng, Yang
AU - Ge, Jingjing
AU - Zhang, Danying
AU - Bai, Xue
AU - Fang, Hongming
AU - Zhou, Yujuan
AU - Che, Wanlin
AU - Zhang, Wenxuan
AU - Zhao, Ruixia
AU - Qiu, Zuchun
AU - Zhao, Xuewei
AU - Xiao, Li
AU - He, Huimin
AU - Cheng, Sinan
AU - Duan, Wei
AU - Wang, Ruiju
AU - Chen, Wei
AU - Nie, Guochao
AU - Hou, Yingchun
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/8
Y1 - 2023/8
N2 - Esophageal squamous cell carcinoma (ESCC) is one of the most popular cancers in digestive tract. Chemotherapy is still the primary treatment for ESCC patients with or without surgery. But the efficacy of the current chemotherapy for ESCC is poor with side effects because of none or weak ESCC targeting and multidrug resistance (MDR). To develop a novel targeting peptide for ESCC targeting diagnosis and therapy, a novel peptide, ESCP9 was screened from a 12-mer phage displayed peptide library. The satisfied sensitivity and specificity of ESCP9 binding to ESCC were characterized with cellular and tissue assays under fluorescence microscope, and by flow cytometry. By the assay of molecular docking, protein kinase C (PKC) was predicted as the target ESCP9 binding to. To develop a novel ESCC targeted and MDR inhibited doxorubicin (DOX) liposomal delivery formulation for ESCC targeting chemotherapy, the DOX delivery formulation (ESCP9-Lipo-DOX-miR101) was synthesized and characterized by using ESCP9 as ESCC directing fragment and miRNA101 as MDR suppressor. Finally, the therapeutic efficacy of the drug formulation for ESCC therapy was primarily evaluated by the therapeutic assay for the wild type and DOX resistant ESCC cells in vitro. The results demonstrated that the drug formulation enhanced cytotoxicity to Eca-109 cells and DOX-resistant Eca-109 cells (Eca-109/ADR) significantly. It is concluded that ESCP9 is a targeting peptide with high specificity and sensitivity, and the ESCP9 conjugated DOX liposomal formulation, ESCP9-Lipo-DOX-miR101, is of the potential to be further studied as an efficient drug formulation for ESCC and DOX resistant ESCC chemotherapy in future.
AB - Esophageal squamous cell carcinoma (ESCC) is one of the most popular cancers in digestive tract. Chemotherapy is still the primary treatment for ESCC patients with or without surgery. But the efficacy of the current chemotherapy for ESCC is poor with side effects because of none or weak ESCC targeting and multidrug resistance (MDR). To develop a novel targeting peptide for ESCC targeting diagnosis and therapy, a novel peptide, ESCP9 was screened from a 12-mer phage displayed peptide library. The satisfied sensitivity and specificity of ESCP9 binding to ESCC were characterized with cellular and tissue assays under fluorescence microscope, and by flow cytometry. By the assay of molecular docking, protein kinase C (PKC) was predicted as the target ESCP9 binding to. To develop a novel ESCC targeted and MDR inhibited doxorubicin (DOX) liposomal delivery formulation for ESCC targeting chemotherapy, the DOX delivery formulation (ESCP9-Lipo-DOX-miR101) was synthesized and characterized by using ESCP9 as ESCC directing fragment and miRNA101 as MDR suppressor. Finally, the therapeutic efficacy of the drug formulation for ESCC therapy was primarily evaluated by the therapeutic assay for the wild type and DOX resistant ESCC cells in vitro. The results demonstrated that the drug formulation enhanced cytotoxicity to Eca-109 cells and DOX-resistant Eca-109 cells (Eca-109/ADR) significantly. It is concluded that ESCP9 is a targeting peptide with high specificity and sensitivity, and the ESCP9 conjugated DOX liposomal formulation, ESCP9-Lipo-DOX-miR101, is of the potential to be further studied as an efficient drug formulation for ESCC and DOX resistant ESCC chemotherapy in future.
KW - Doxorubicin
KW - Esophageal squamous cell carcinoma
KW - MiR-101
KW - Targeting chemotherapy
KW - Targeting peptide
UR - http://www.scopus.com/inward/record.url?scp=85165399933&partnerID=8YFLogxK
U2 - 10.1016/j.mtadv.2023.100407
DO - 10.1016/j.mtadv.2023.100407
M3 - Article
AN - SCOPUS:85165399933
SN - 2590-0498
VL - 19
JO - Materials Today Advances
JF - Materials Today Advances
M1 - 100407
ER -
