Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells.

Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells.
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DOI:
10.1039/c5nr04867b
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发表时间:
2015-11-21
期刊:
影响因子:
6.7
通讯作者:
Zhang M
Zhang M
中科院分区:
材料科学2区
文献类型:
--
作者:
Mu Q;Kievit FM;Kant RJ;Lin G;Jeon M;Zhang M

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用于靶向治疗的纳米颗粒(NPs)需要具有适当的尺寸、稳定性、药物负载和释放特性以及有效的靶向配体。然而,许多现有的纳米颗粒如白蛋白、脂质体、聚合物、金纳米颗粒等在装载药物、荧光团和靶向配体时遇到尺寸限制、毒性和稳定性问题。此外,抗体体积庞大,并且可以极大地影响NP的物理化学性质,而许多基于小分子的靶向配体缺乏特异性。在这里,我们报告了利用生物相容性、生物可降解性、小(~30 nm)和稳定的氧化铁纳米颗粒(IONP),使用抗HER 2/neu肽(AHNP)靶向配体将紫杉醇(PTX)靶向递送至HER 2/neu阳性乳腺癌。我们证明了这些纳米颗粒在生物介质中的均匀尺寸和高稳定性,在活小鼠中的有效肿瘤靶向,以及它们在人HER 2/neu阳性乳腺癌细胞中的有效细胞靶向和选择性杀伤。
Nanoparticles (NPs) for targeted therapy are required to have appropriate size, stability, drug loading and release profiles, and efficient targeting ligands. However, many of existing NPs such as albumin, liposomes, polymers, gold NPs, etc. encounter size limit, toxicity and stability issues when loaded with drugs, fluorophores, and targeting ligands. Furthermore, antibodies are bulky and can greatly affect the physicochemical properties of the NPs, whereas many small molecule-based targeting ligands lack specificity. Here, we report utilization of biocompatible, biodegradable, small (~30 nm) and stable iron oxide NPs (IONPs) for targeted delivery of paclitaxel (PTX) to HER2/neu positive breast cancer using an anti-HER2/neu peptide (AHNP) targeting ligand. We demonstrate the uniform size and high stability of these NPs in biological medium, effective tumour targeting in live mice, as well as their efficient cellular targeting and selective killing in human HER2/neu-positive breast cancer cells.