紫杉醇
PEG比率
共轭体系
化学
结合
纳米医学
胶体金
聚乙二醇
生物相容性
聚乙二醇化
体内
药物输送
药品
组合化学
药理学
生物物理学
纳米颗粒
纳米技术
材料科学
生物化学
有机化学
化疗
聚合物
医学
数学分析
外科
数学
财务
生物技术
经济
生物
作者
Huaisong Wang,Lin Wang,Yueyuan Gao,Ya Ding
标识
DOI:10.1016/j.cclet.2020.08.044
摘要
Structure-efficacy effect of small molecular drug attracts wide attentions, but it has always been ignored in nanomedicine research. To reveal the efficacy modulation of nanomedicine, we developed a new type of paclitaxel (PTX)-conjugated gold nanoparticles (PTX-conjugated GNPs) to investigate the influence of drug position in controlling their in vitro properties and in vivo performance. Two therapeutic ligands (TA-PEG-NH-N=PTX and TA-PTX=N-NH-PEG) were synthesized to conjugate PTX on the surface of GNPs at different positions, locating on the surface of gold conjugate and inserting between GNPs and polyethylene glycol (PEG, molecular weight 1000 Da), respectively. It was found that [email protected] with PTX located between GNP and PEG exhibited higher aqueous solubility, biocompatibility, and stability. In addition, an acid sensitive hydrazone bond has been inserted between PTX and PEG in both ligands for drug release of PTX and PTX-PEG segment, respectively, at the tumor site. Further release of PTX from PTX-PEG segment is based on the esterase hydrolysis of an ester bond between PTX and PEG. This two-step drug release mechanism offers [email protected] effective and sustained release behavior for desirable anticancer activity, enhanced therapeutic efficacy, and lower systematic toxicity in Heps-bearing animal models.
科研通智能强力驱动
Strongly Powered by AbleSci AI