Targeted non-covalent self-assembled nanoparticles based on human serum albumin.

Targeted non-covalent self-assembled nanoparticles based on human serum albumin.
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DOI:
10.1016/j.biomaterials.2011.10.005
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发表时间:
2012-01
期刊:
影响因子:
14
通讯作者:
van Leeuwen, Fijs W. B.
van Leeuwen, Fijs W. B.
中科院分区:
工程技术1区
文献类型:
--
作者:
Bunschoten, Anton;Buckle, Tessa;Kuil, Joeri;Luker, Gary D.;Luker, Kathryn E.;Nieweg, Omgo E.;van Leeuwen, Fijs W. B.

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人血清白蛋白(HSA)是一种生物纳米载体,它与许多合成分子和生物分子形成非共价复合物。先前我们证明,放射性标记的基于HSA的纳米粒子可与荧光菁染料形成非共价复合物,产生用于肿瘤引流淋巴结手术导航的成像剂。在此,自组装方法实现了快速的临床转化。基于这一经验,我们推断将这种非共价技术扩展到靶向方法会很有趣。我们探索了HSA通过近红外(NIR)菁染料与肽形成非共价自组装复合物的能力。利用HSA - Cy5与非共价结合的荧光分子吲哚菁绿(ICG)、IR783 - CO₂H以及三种IR783标记的靶向肽之间的福斯特共振能量转移(FRET)猝灭相互作用来监测复合物的组装和拆卸。HSA与IR783标记的肽之间的主 - 客体相互作用使得能够形成(生物)纳米粒子,其表面覆盖有可能靶向αvβ3 - 整合素、趋化因子受体4(CXCR4)和生长抑素受体的肽。展示了CXCR4靶向(生物)纳米粒子在前哨淋巴结手术中的潜力。通过将近红外染料标记的肽非共价结合到一种已获临床批准的HSA支架上,我们很容易地形成了靶向生物纳米粒子。
Human serum albumin (HSA) is a biological nanocarrier that forms non-covalent complexes with a number of synthetic and biomolecules. Previously we demonstrated radiolabeled HSA-based nanoparticles can form non-covalent complexes with fluorescent cyanine dyes yielding imaging agents for surgical guidance towards tumor draining lymph nodes. Here the self-assembly approach enabled rapid clinical translation. Based on this experience we reasoned it would be interesting to expand this non-covalent technology to a targeted approach. The ability of HSA to form non-covalent self-assembled complexes with peptides via near-infrared (NIR) cyanine dyes was explored. Föster resonance energy transfer (FRET) quenching interactions between HSA-Cy5 and the non-covalently bound fluorescent molecules indocyanine green (ICG), IR783-CO2H and three IR783-labeled targeting peptides were used to monitor complex assembly and disassembly. The host-guest interactions between HSA and IR783-labeled peptides enabled the formation of (bio)nanoparticles that are coated with peptides that may target αvβ3-integrins, the chemokine receptor 4 (CXCR4), and somatostatin receptors. The potential of CXCR4-targeted (bio)nanoparticles in sentinel lymph node procedures is demonstrated. By non-covalently binding NIR-dye labeled peptides to an already clinically approved HSA-scaffold, we have readily formed targeted bionanoparticles.
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