Multidentate Catechol-Based Polyethylene Glycol Oligomers Provide Enhanced Stability and Biocompatibility to Iron Oxide Nanoparticies
Multidentate Catechol-Based Polyethylene Glycol Oligomers Provide Enhanced Stability and Biocompatibility to Iron Oxide Nanoparticies
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DOI：
10.1021/nn203735b
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发表时间：
2012-01-01
期刊：
影响因子：
17.1
通讯作者：
Mattoussi, Hedi
中科院分区：
文献类型：
--
作者：
Na, Hyon Bin;Palui, Goutam;Mattoussi, Hedi
我们已经设计，制备和测试了一组新的多齿儿茶酚和聚乙二醇（PEG）衍生的低聚物，寡聚乙二醇-多巴，作为配体，表现出很强的亲和力，氧化铁纳米晶体。配体由短的聚（丙烯酸酯）主链组成，该主链横向附加有几个儿茶酚锚定基团和几个末端官能化的PEG部分，以促进对水性介质的亲和力并允许进一步偶联至靶分子（生物和其他）。这些多配位聚乙二醇化低聚物使用基于N，N '-二环己基碳二亚胺（DCC）和N-（3-二甲基氨基丙基）-N'-乙基碳二亚胺（EDC）缩合的相对简单的化学策略制备。将这些儿茶酚官能化的低聚物赋予纳米颗粒长期胶体稳定性的能力与其他对照配体（即，呈现几个羧基的低聚物和呈现一个儿茶酚或一个羧基的单齿配体）进行比较。我们发现，寡聚PEG-Dopa配体提供快速的配体交换，并且所得纳米颗粒在宽pH范围内和在过量电解质存在下表现出极大增强的胶体稳定性;与非儿茶酚呈递分子或寡聚体配体相比，稳定性显著改善。通过插入可控部分的叠氮化物封端的PEG部分，纳米颗粒（NP）通过叠氮化物-炔环加成（Click）变得与互补官能团反应，这开辟了这种稳定NP的生物靶向的可能性。特别地，我们测试了助剂（叠氮化物官能化的纳米颗粒与炔改性的染料的偶联）。我们还测量了OligoPEG封端的Fe 3 O 4纳米颗粒的MRI T-2对比度，并应用MTT（3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物）测定来测试这些纳米颗粒对活细胞的潜在细胞毒性;我们发现对活细胞没有可测量的毒性。
We have designed, prepared, and tested a new set of multidentate catechol- and polyethylene glycol (PEG)-derivatized oligomers, OligoPEG-Dopa, as ligands that exhibit strong affinity to iron oxide nanocrystals. The ligands consist of a short poly(acrylic add) backbone laterally appended with several catechol anchoring groups and several terminally functionalized PEG moieties to promote affinity to aqueous media and to allow further coupling to target molecules (bio and others). These multicoordinating PEGylated oligomers were prepared using a relatively simple chemical strategy based on N,N'-dicyclohexylcarbodiimide (DCC) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) condensation. The ability of these catechol-functionalized oligomers to impart long-term colloidal stability to the nanoparticles is compared to other control ligands, namely, oligomers presenting several carboxyl groups and monodentate ligands presenting either one catechol or one carboxyl group. We found that the OligoPEG-Dopa ligands provide rapid ligand exchange, and the resulting nanoparticles exhibit greatly enhanced colloidal stability over a broad pH range and in the presence of excess electrolytes; stability is notably improved compared to non-catechol presenting molecular or oligomer ligands. By inserting controllable fractions of azide-terminated PEG moieties, the nanoparticles (NPs) become reactive to complementary functionalities via azide-alkyne cycloaddition (Click), which opens up the possibility of biological targeting of such stable NPs. In particular, we tested the aid( coupling of azide-functionalized nanoparticles to an alkyne-modified dye. We also measured the MRI T-2 contrast of the OligoPEG-capped Fe3O4 nanoparticles and applied MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to test the potential cytotoxicity of these NPs to live cells; we found no measurable toxicity to live cells.