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用于将紫杉醇靶向递送至乳腺癌细胞的抗HER2/neu肽偶联氧化铁纳米颗粒。

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

作者信息

Mu Qingxin, Kievit Forrest M, Kant Rajeev J, Lin Guanyou, Jeon Mike, Zhang Miqin

机构信息

Departments of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.

Department of Neurological Surgery, University of Washington, Seattle, Washington 98195, USA.

出版信息

Nanoscale. 2015 Nov 21;7(43):18010-4. doi: 10.1039/c5nr04867b.

Abstract

Nanoparticles (NPs) for targeted therapy are required to have appropriate size, stability, drug loading and release profiles, and efficient targeting ligands. However, many of the 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 this can greatly affect the physicochemical properties of the NPs, whereas many small molecule-based targeting ligands lack specificity. Here, we report the 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 cells using an anti-HER2/neu peptide (AHNP) targeting ligand. We demonstrate the uniform size and high stability of these NPs in biological medium, their effective tumour targeting in live mice, as well as their efficient cellular targeting and selective killing in human HER2/neu-positive breast cancer cells.

摘要

用于靶向治疗的纳米颗粒(NPs)需要具备合适的尺寸、稳定性、药物负载和释放特性,以及高效的靶向配体。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,在负载药物、荧光团和靶向配体时会遇到尺寸限制、毒性和稳定性问题。此外,抗体体积较大,这会极大地影响纳米颗粒的物理化学性质,而许多基于小分子的靶向配体缺乏特异性。在此,我们报道了利用生物相容性好、可生物降解、尺寸小(约30纳米)且稳定的氧化铁纳米颗粒(IONPs),通过抗HER2/neu肽(AHNP)靶向配体将紫杉醇(PTX)靶向递送至HER2/neu阳性乳腺癌细胞。我们展示了这些纳米颗粒在生物介质中的均匀尺寸和高稳定性、它们在活体小鼠中的有效肿瘤靶向性,以及它们在人HER2/neu阳性乳腺癌细胞中的高效细胞靶向性和选择性杀伤作用。

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