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自组装壳聚糖聚合物插层肽功能化金纳米粒子作为纳米探针,用于癌症诊断中尿激酶型纤溶酶原激活物受体的高效成像。

Self-assembled chitosan polymer intercalating peptide functionalized gold nanoparticles as nanoprobe for efficient imaging of urokinase plasminogen activator receptor in cancer diagnostics.

机构信息

DBT-National Institute of Animal Biotechnology (DBT-NIAB), Hyderabad 500032, Telangana, India.

Amity Institute of Biotechnology, Amity University Haryana, Manesar, Panchgaon, Haryana 122413, India.

出版信息

Carbohydr Polym. 2021 Aug 15;266:118138. doi: 10.1016/j.carbpol.2021.118138. Epub 2021 Apr 30.

DOI:10.1016/j.carbpol.2021.118138
PMID:34044952
Abstract

Targeting cell surface receptors for specific drug delivery in cancer has garnered lot of attention. Urokinase plasminogen activator receptor (uPAR), a surface biomarker, is overexpressed on many tumours including breast, colorectal, prostate, and ovarian cancers. Binding of growth factor domain (GFD) of urokinase plasminogen activator (uPA) with uPAR lead to its close conformation, and allow somatomedin B domain (SMB) of vitronectin binding by allosteric modulation. In-silico docking of uPAR with GFD and SMB peptides was performed to identify potential binding affinity. Herein, we report fluorescently labeled peptide functionalized AuNPs with a mixed self-assembled monolayer of intercalating chitosan polymer for efficient targeting and imaging of uPAR-positive cells. The biophysical characterization of nanoconjugates and uPAR-specific targeting was assessed by FACS, cell adhesion, and fluorescence imaging. AuNPs/chitosan/GFD+SMB peptides showed higher uptake as compared to AuNPs/chitosan/GFD, and AuNPs/chitosan/SMB that can be utilized as a tool for molecular targeting and imaging in metastasis.

摘要

针对细胞表面受体的特定药物输送在癌症治疗中受到了广泛关注。尿激酶型纤溶酶原激活物受体(uPAR)是一种表面生物标志物,在许多肿瘤中过度表达,包括乳腺癌、结直肠癌、前列腺癌和卵巢癌。尿激酶纤溶酶原激活物(uPA)的生长因子结构域(GFD)与 uPAR 的结合导致其紧密构象,并通过别构调节允许结合 vitronectin 的 somatomedin B 结构域(SMB)。通过计算机对接研究了 uPAR 与 GFD 和 SMB 肽的结合,以鉴定潜在的结合亲和力。在此,我们报告了用混合自组装壳聚糖聚合物功能化的荧光标记肽的 AuNPs,用于靶向和成像 uPAR 阳性细胞。通过 FACS、细胞黏附和荧光成像评估了纳米复合物的生物物理特性和 uPAR 特异性靶向。与 AuNPs/chitosan/GFD 和 AuNPs/chitosan/SMB 相比,AuNPs/chitosan/GFD+SMB 肽具有更高的摄取率,可作为转移中分子靶向和成像的工具。

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