典型文献
Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer
文献摘要：
Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addi-tion,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSA-LDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2％and 94.8％,respectively(P＜0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.
文献关键词：
中图分类号：
作者姓名：
Yang-Yang Wang;Liang Li;Xiu-Jun Liu;Qing-Fang Miao;Yi Li;Meng-Ran Zhang;Yong-Su Zhen
作者机构：
Department of Pediatric Oncology,Tianjin Medical University Cancer Institute and Hospital,Tianjin,300060,China;NHC Key Laboratory of Biotechnology of Antibiotics,Department of Oncology,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China
文献出处：
引用格式：
[1]Yang-Yang Wang;Liang Li;Xiu-Jun Liu;Qing-Fang Miao;Yi Li;Meng-Ran Zhang;Yong-Su Zhen-.Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer)[J].药物分析学报（英文）,2022(02):232-242
A类：
bioconjugate,desmoplasia,apoprotein,lidamycin,enediyne,AsPc
B类：
Development,novel,multi,functional,integrated,effectively,targeting,Ras,mutant,pancreatic,Folate,receptor,FR,overexpression,occurs,variety,cancers,including,In,addi,enhanced,macropinocytosis,exists,Furthermore,occurrence,intensive,causes,hypoxic,microenvironment,this,study,directed,highly,folate,human,serum,albumin,HSA,LDP,active,AE,derived,from,was,designed,prepared,consisted,four,moieties,presented,binding,efficiency,cells,Its,uptake,wild,extensive,than,By,vivo,optical,imaging,displayed,prominent,tumor,specific,biodistribution,bearing,mice,showing,clear,lasting,localization,MTT,assay,demonstrated,potent,cytotoxicity,three,types,lines,also,induced,apoptosis,caused,G2,cycle,arrest,markedly,suppressed,growth,xenografts,athymic,At,well,tolerated,doses,twice,inhibition,rates,were,respectively,results,indicate,that,might,treating
AB值：
0.508828
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
