Facile, efficient approach to accomplish tunable chemistries and variable biodistributions for shell cross-linked nanoparticles
Facile, efficient approach to accomplish tunable chemistries and variable biodistributions for shell cross-linked nanoparticles
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DOI：
10.1021/bm800246x
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发表时间：
2008-07-01
影响因子：
6.2
通讯作者：
Welch, Michael J.
中科院分区：
文献类型：
--
作者：
Sun, Guorong;Hagooly, Aviv;Welch, Michael J.
壳交联的膝状（SCK）纳米粒子的体内行为被证明是可调的，通过一个简单的和多功能的过程，在纳米医学领域的有吸引力的纳米级载体的进步SCK。通过将不同数量的甲氧基封端的聚（乙二醇）（mPEG）链接枝到两亲性嵌段共聚物前体上，以及用于放射性示踪剂和治疗剂Cu-64的螯合剂，然后自组装成嵌段共聚物胶束并在整个壳区域进行化学交联来完成药代动力学的调节。然后进行Cu-64-放射性标记以通过生物分布实验和正电子发射断层扫描（PET）来评估体内SCKs。结果发现，聚乙二醇化的SCK的血液滞留可以被调节，这取决于mPEG接枝密度和纳米颗粒表面性质。作为体内行为的函数的mPEG表面覆盖的密度的半定量模型被施加到增强对该系统的理解。
The in vivo behavior of shell cross-linked knedel-like (SCK) nanoparticles is shown to be tunable via a straightforward and versatile process that advances SCKs as attractive nanoscale carriers in the field of nanomedicine. Tuning of the pharmacokinetics was accomplished by grafting varied numbers of methoxy-terminated poly(ethylene glycol) (mPEG) chains to the amphiphilic block copolymer precursors, together with chelators for the radioactive tracer and therapeutic agent Cu-64, followed by self-assembly into block copolymer micelles and chemical cross-linking throughout the shell regions. Cu-64-radiolabeling was then performed to evaluate the SCKs in vivo by means of biodistribution experiments and positron emission tomography (PET). It was found that the blood retention of PEGylated SCKs could be tuned, depending on the mPEG grafting density and the nanoparticle surface properties. A semiquantitative model of the density of mPEG surface coverage as a function of in vivo behavior was applied to enhance the understanding of this system.