Double Click: Dual Functionalized Polymeric Micelles with Antibodies and Peptides
Double Click: Dual Functionalized Polymeric Micelles with Antibodies and Peptides
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DOI：
10.1021/bc300511a
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发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Shoichet, Molly S.
中科院分区：
文献类型：
--
作者：
Chan, Dianna P. Y.;Owen, Shawn C.;Shoichet, Molly S.
聚合物纳米粒子胶束提供了一个可能的平台，治疗诊断交付，结合在一个车辆的治疗和诊断的作用。为了探索双功能胶束，将聚（D，L-丙交酯-co-2-甲基-2-羧基三亚甲基碳酸酯）-graft-poly（ethylene glycol）-X（P（LA-co-TMCC）-g-PEG-X）两亲性共聚物自组装成胶束，X代表叠氮化物或呋喃。P（LA-co-TMCC）-g-PEG-叠氮化物和P（LA-co-TMCC）-g-PEG-呋喃末端官能团的胶束分别用于缀合二苄基环辛炔和马来酰亚胺修饰的探针，利用正交偶联化学。为了验证双功能胶束的效用，通过连续点击化学反应共价结合曲妥珠单抗-马来酰亚胺抗体和FLAG-二苄基环辛炔肽。用双官能化胶束处理的SKOV-3luc细胞通过共聚焦成像显示抗体和肽的共定位，证明了这种方法的前景。
Polymeric nanoparticle micelles provide a possible platform for theranostic delivery, combining the role of therapeutics and diagnostics in one vehicle. To explore dual-functional micelles, the amphiphilic copolymer of poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol)-X (P(LA-co-TMCC)-g-PEG-X) was self-assembled to form micelles, with X representing either azide or furan. Micelles of P(LA-co-TMCC)-g-PEG-azide and P(LA-co-TMCC)-g-PEG-furan terminal functional groups were used to conjugate dibenzylcyclooctyne and maleimide-modified probes, respectively, taking advantage of orthogonal coupling chemistry. To verify the utility of the dual-functional micelles, trastuzumab-maleimide antibodies and FLAG-dibenzylcyclooctyne peptides were covalently bound by sequential click chemistry reactions. SKOV-3luc cells that were treated with the dual-functionalized micelles showed colocalization of the antibodies and peptides by confocal imaging, demonstrating the promise of this approach.