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Development of Anti-HER2 Conjugated ICG-loaded Polymeric Nanoparticles for Targeted Optical Imaging of Ovarian Cancer

机译:抗HER2共轭ICG负载的聚合物纳米粒子的卵巢癌靶向光学成像的发展。

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Targeted delivery of therapeutic and imaging agents using surface modified nanovectors has been explored immensely in recent years. The growing demand for site-specific and efficient delivery of nanovectors entails stable surface conjugation of targeting moieties. We have developed a polymeric nanocapsule doped with Indocyanine green (ICG) with potential for targeted and deep tissue optical imaging and phototherapy. Our ICG-loaded nanocapsules (ICG-NCs) have potential for covalent coupling of various targeting moieties and materials due to presence of amine groups on the surface. Here, we covalently bioconjugate polyethylene glycol(PEG)-coated ICG-NCs with monoclonal antibody against HER2 through reductive amination-mediated procedures. The irreversible and stable bonds are formed between anti-EGFR and aldehyde termini of PEG chains on the surface of ICG-NCs. We confirm the uptake of conjugated ICG-NCs by ovarian cancer cells over-expressing HER2 using fluorescent confocal microscopy. The proposed process for covalent attachment of anti-HER2 to PEGylated ICG-NCs can be used as a methodology for bioconjugation of various antibodies to such nano-constrcuts, and provides the capability to use these optically active nano-probes for targeted optical imaging of ovarian and other cancer types.
机译:近年来,已经对使用表面修饰的纳米载体的治疗剂和显像剂的靶向递送进行了深入研究。对位点特异性和有效递送纳米载体的需求增长,使得靶向部分的表面稳定结合。我们已经开发了掺杂有吲哚菁绿(ICG)的聚合物纳米胶囊,具有针对性和深层组织光学成像和光疗的潜力。由于表面上存在胺基,我们的装有ICG的纳米胶囊(ICG-NC)具有与各种靶向部分和材料共价偶联的潜力。在这里,我们通过还原胺化介导的程序与抗HER2的单克隆抗体共价偶联生物共轭聚乙二醇(PEG)涂层的ICG-NC。在ICG-NC的表面上,抗EGFR和PEG链的醛末端之间形成不可逆且稳定的键。我们通过荧光共聚焦显微镜证实过度表达HER2的卵巢癌细胞摄取结合的ICG-NCs。所提出的将抗HER2共价附于聚乙二醇化ICG-NC的方法可用作将各种抗体生物缀合至此类纳米结构的方法,并提供使用这些光学活性纳米探针进行卵巢靶向光学成像的能力和其他癌症类型。

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