Synthesis and In Vivo Pharmacokinetic Evaluation of Degradable Shell Cross-Linked Polymer Nanoparticles with Poly(carboxybetaine) versus Poly(ethylene glycol) Surface-Grafted Coatings
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- 作者：Ang Li ; Hannah P. Luehmann ; Guorong Sun ; Sandani Samarajeewa ; Jiong Zou ; Shiyi Zhang ; Fuwu Zhang ; Michael J. Welch ; Yongjian Liu ; Karen L. Wooley
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：October 23, 2012
- 年：2012
- 卷：6
- 期：10
- 页码：8970-8982
- 全文大小：735K
- 年卷期：v.6,no.10(October 23, 2012)
- ISSN：1936-086X
文摘
Nanoparticles with tunable pharmacokinetics are desirable for various biomedical applications. Poly(ethylene glycol) (PEG) is well-known to create 鈥渟tealth鈥?effects to stabilize and extend the blood circulation of nanoparticles. In this work, poly(carboxybetaine) (PCB), a new nonfouling polymer material, was incorporated as surface-grafted coatings, conjugated onto degradable shell cross-linked knedel-like nanoparticles (dSCKs) composed of poly(acrylic acid)-based shells and poly(lactic acid) cores, to compare the in vivo pharmacokinetics to their PEG-functionalized analogues. A series of five dSCKs was prepared from amphiphilic block copolymers, having different numbers and lengths of either PEG or PCB grafts, by supramolecular assembly in water followed by shell cross-linking, and then studied by a lactate assay to confirm their core hydrolytic degradabilities. Each dSCK was also conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocyclic chelators and tyramine moieties to provide for 64Cu and/or radiohalogen labeling. The high specific activity of 64Cu radiolabeling ensured nanogram administration of dSCKs for in vivo evaluation of their pharmacokinetics. Biodistribution studies demonstrated comparable in vivo pharmacokinetic profiles of PCB-grafted dSCKs to their PEG-conjugated counterparts. These results indicated that PCB-functionalized dSCKs have great potential as a theranostic platform for translational research.