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Sci.Rep:浙大药学院陈枢青研究组发表肿瘤最新研究成果

摘要 : 10月8日,自然出版集团旗下期刊Scientific Reports上发表了浙江大学药学院陈枢青教授课题组题为《Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities》的研究论文,论文第一作者为潘利强博士。

10月8日,自然出版集团旗下期刊Scientific Reports上发表了浙江大学药学院陈枢青教授课题组题为《Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities》的研究论文,论文第一作者为潘利强博士。

该论文在课题组前期研究基础上(Pan LQ, et al, Adv Mater, 25(34), 4718-4722.; Pan LQ, et al, Biomaterials, 34(36), 9115-9123.),利用空间位阻效应对肿瘤坏死因子凋亡诱导配体(TRAIL)三聚体进行了双重异质修饰,同时将聚乙二醇(PEG)和海兔毒素(MMAE)与TRAIL三聚体在同一突变位点偶联,从而达到同步增强PK/PD的效果,提高了TRAIL在裸鼠荷瘤模型体内的抗肿瘤效果。其中,MMAE可发挥与TRAIL胞外凋亡传导通路迥异的凋亡机制,通过与TRAIL偶联可被靶向至肿瘤部位,克服部分肿瘤细胞的TRAIL耐受。

原文链接:

Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities

原文摘要:

Poor pharmacokinetics and resistance within some tumor cell lines have been the major obstacles during the preclinical or clinical application of TRAIL (tumor-necrosis-factor (TNF)-related apoptosis-inducing ligand). The half-life of TRAIL114-281 (114 to 281 amino acids) was revealed to be no more than 30 minutes across species. Therefore maleimido activated PEG (polyethylene glycol) and MMAE (Monomethyl Auristatin E) were applied to site-specifically conjugate with the mutated cysteines from different monomers of TRAIL successively, taking advantage of steric effects involved within TRAIL mutant conjugations. As a result, TRAIL trimer was hetero-modified for different purposes. And the resulting PEG-TRAIL-vcMMAE conjugate exhibited dramatically improved half-life (11.54 h), favourable in vivo targeting capability and antitumor activities while no sign of toxicity in xenograft models, suggesting it’s a viable therapeutic and drug delivery strategy.

来源: Scientific Reports 浏览次数:0

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