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Carboxyl Group (-CO2H) Functionalized Coordination Polymer Nanoparticles as Efficient Platforms for Drug Delivery

机译:羧基 (-CO2H) 功能化配位聚合物纳米颗粒作为药物递送的高效平台

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摘要

Functionalization of nanoparticles can significantly influence their properties and potential applications. Although researchers can now functionalize metal, metal oxide, and organic polymer nanoparticles with a high degree of precision, controlled surface functionalization of nanoscale coordination polymer particles (CPPs) has remained a significant challenge. The lack of methodology is perhaps one of the greatest roadblocks to the advancement of CPPs into high added-value drug delivery applications. Here, we report having achieved this goal through a stepwise formation and functionalization protocol. We fabricated robust nanoparticles with enhanced thermal and colloidal stabilities by incorporation of carboxyl groups and these surface carboxyl groups could be subsequently functionalized through well-known peptide coupling reactions. The set of chemistries that we employed as proof-of-concept enabled a plethora of new functional improvements for the application of CPPs as drug delivery carriers, including enhanced colloidal stabilities and the incorporation of additional functional groups such as polyethylene glycol (PEG) or fluorescent dyes that enabled tracking of their cellular uptake. Finally, we ascertained the cytotoxicity of the new CPP nanoparticles loaded with camptothecin to human breast adenocarcinoma (MCF-7). Efflux measurements show that the encapsulation of camptothecin enhances the potency of the drug 6.5-fold and increases the drug retention within the cell.
机译:纳米颗粒的功能化可以显着影响其性质和潜在应用。尽管研究人员现在可以高精度地对金属、金属氧化物和有机聚合物纳米颗粒进行功能化,但纳米级配位聚合物颗粒 (CPP) 的受控表面功能化仍然是一个重大挑战。缺乏方法可能是将CPP推进到高附加值药物递送应用的最大障碍之一。在这里,我们报告了通过逐步形成和功能化协议实现了这一目标。我们通过掺入羧基制备了具有增强热稳定性和胶体稳定性的坚固纳米颗粒,这些表面羧基随后可以通过众所周知的肽偶联反应进行官能化。我们用作概念验证的一组化学试剂为CPP作为药物递送载体的应用提供了大量新的功能改进,包括增强胶体稳定性和掺入其他官能团,如聚乙二醇(PEG)或荧光染料,从而能够跟踪其细胞摄取。最后,我们确定了负载喜树碱的新型CPP纳米颗粒对人乳腺癌(MCF-7)的细胞毒性。外排测量表明,喜树碱的包封使药物的效力提高 6.5 倍,并增加细胞内的药物保留。

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