项目名称: 肿瘤靶向多肽纳米纤维作为疏水性抗肿瘤药物载体的研究
项目编号: No.51303213
项目类型: 青年科学基金项目
立项/批准年度: 2014
项目学科: 一般工业技术
项目作者: 杨翠红
作者单位: 中国医学科学院
项目金额: 25万元
中文摘要: 自组装纳米药物载体在药物缓控释及靶向传输方面已经发挥了巨大推动作用。研究证实,除化学组成,尺寸大小及表面电位等因素外,形状对于纳米载体体内代谢也具有重要影响。对于某些载体材料,纳米纤维比纳米球表现出更少的网状内皮系统摄取和更强的肿瘤组织选择性。多肽纳米材料因生物相容性好,易连接功能基团,且可以根据需要自下而上地设计序列而被广泛应用。自组装多肽纳米纤维在药物传输领域具有很大的应用前景。因此本项目拟设计多种肿瘤靶向性的多肽分子,与疏水性抗肿瘤药物如10-羟基喜树碱共组装形成可注射的纳米纤维。采用放射性核素碘[125]标记研究靶向与非靶向以及不同氨基酸构型对多肽纤维载体的体内分布及肿瘤组织靶向性的影响。最终通过体内外肿瘤靶向治疗研究来开发一种具有肿瘤靶向性、提高疏水药物溶解度、降低毒副作用和提高生物利用度的多肽纳米纤维药物载体。本研究将为肿瘤的靶向治疗及临床疏水性药物的应用提供新的思路和方法。
中文关键词: 自组装多肽;纳米纤维;D-构型氨基酸;肿瘤靶向;
英文摘要: Self-assembled nano-drug carriers have been intensitively applied in controlled drug release and targeting drug delivery. In addition to the chemical composition, size, surface potential and other factors, recent researches have confirmed that the shape of the nanocarriers plays an important role in their in vivo metabolism. For some types of carriers, nanofibers have less uptake by the reticuloendothelial system (RES) and stronger tumor tissue selectivity than nanospheres. Peptide based nanomaterials have been widely used because of their good biocompatibility, easy modification by functional groups and design flexibility according to the needs through a "bottom-up" approach. Self-assembling peptide nanofiber has great application prospects in the field of drug delivery. In this project, we will design a series of peptide molecules with active tumor-targeting motifs. These targeting peptides could assemble with the hydrophobic anticancer drugs such as 10-hydroxycamptothecin to form injectable nanofibers. We will study the impacts of targeting and nontargeting motifs and amino acid configuration on the biodistribution and tumor targeting capacity of the peptide nanofiber carriers by labeling with radionuclide iodine-125. The in vitro and in vivo anti-tumor experiments will also be involved. We expect to develop
英文关键词: self-assembling peptide;nanofiber;D-amino acid;tumor-targeting;