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新型功能化 Pluronic 纳米胶束偶联抗间皮素抗体用于小动物的无创肿瘤检测。

Non-invasive tumor detection in small animals using novel functional Pluronic nanomicelles conjugated with anti-mesothelin antibody.

机构信息

The Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, The State University of New York at Buffalo, Buffalo, NY 14260, United States.

出版信息

Nanoscale. 2011 Apr;3(4):1813-22. doi: 10.1039/c1nr00001b. Epub 2011 Mar 2.

Abstract

In this study QDs were encapsulated in carboxylated PluronicF127 (F127COOH) triblock polymeric micelles and conjugated with anti-mesothelin antibody for the purpose of alleviating potential toxicity, enhancing the stability and improving targeting efficiency of CdTe/ZnS quantum dots (QDs) in tumors. The amphiphilic triblock polymer of F127COOH contains hydrophilic carboxylated poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) units. After encapsulating QDs into carboxylated F127 (F127COOH-QD) micelles, the particles were conjugated with anti-mesothelin antibodies to allow targeting of cancerous areas. The size of the monodispersed spherical QD-containing micelles was determined to be ∼120 nm by dynamic light scattering (DLS). The critical micelle concentration (CMC) was estimated to be 4.7 × 10(-7) M. In an in vitro study, the anti-methoselin antibody conjugated F127COOH (Me-F127COOH-QD) nanomicelles showed negligible cytotoxicity to pancreatic cancer cells (Panc-1). Confocal microscopy demonstrated that the Me-F127COOH-QD nanomicelles were taken up more efficiently by Panc-1 cells, due to antibody mediated targeting. An in vivo imaging study showed that Me-F127COOH-QD nanomicelles accumulated at the pancreatic tumor site 15 min after intravenous injection. In addition, the low in vivo toxicity of the nanomicellar formulation was evaluated by pathological assays. These results suggest that anti-mesothein antibody conjugated carboxylated F127 nanomicelles may serve as a promising nanoscale platform for early human pancreatic cancer detection and targeted drug delivery.

摘要

在这项研究中,我们将量子点封装在羧基化的 Pluronic F127(F127COOH)三嵌段聚合物胶束中,并与抗间皮素抗体偶联,以减轻潜在的毒性、提高量子点(QDs)在肿瘤中的稳定性和靶向效率。F127COOH 的两亲性三嵌段聚合物含有亲水性羧基化聚(环氧乙烷)(PEO)和疏水性聚(环氧丙烷)(PPO)单元。将 QDs 封装到羧基化的 F127(F127COOH-QD)胶束中后,将这些颗粒与抗间皮素抗体偶联,以实现对癌区的靶向。通过动态光散射(DLS)测定单分散球形含 QD 胶束的粒径约为 120nm。临界胶束浓度(CMC)估计为 4.7×10(-7)M。在体外研究中,抗间皮素抗体偶联的 F127COOH(Me-F127COOH-QD)纳米胶束对胰腺癌细胞(Panc-1)几乎没有细胞毒性。共聚焦显微镜显示,由于抗体介导的靶向作用,Me-F127COOH-QD 纳米胶束被 Panc-1 细胞更有效地摄取。体内成像研究表明,静脉注射后 15min,Me-F127COOH-QD 纳米胶束在胰腺肿瘤部位积聚。此外,通过病理分析评估了纳米胶束制剂的低体内毒性。这些结果表明,抗间皮素抗体偶联的羧基化 F127 纳米胶束可作为一种有前途的纳米级平台,用于早期人类胰腺癌的检测和靶向药物递送。

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