抗体功能化金纳米粒子作为质子治疗的肿瘤靶向增敏剂。

Antibody-functionalized gold nanoparticles as tumor-targeting radiosensitizers for proton therapy.

机构信息

Research Center for the Physics of Matter & Radiation (PMR-LARN), Namur Research Institute for Life Sciences (NARILIS), University of Namur, B-5000 Namur, Belgium.

Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, B-5000 Namur, Belgium.

出版信息

Nanomedicine (Lond). 2019 Feb;14(3):317-333. doi: 10.2217/nnm-2018-0161. Epub 2019 Jan 24.

DOI:10.2217/nnm-2018-0161

PMID:30675822

Abstract

AIM

This study aimed at developing antibody-functionalized gold nanoparticles (AuNPs) to selectively target cancer cells and probing their potential radiosensitizing effects under proton irradiation.

MATERIALS & METHODS: AuNPs were conjugated with cetuximab (Ctxb-AuNPs). Ctxb-AuNP uptake was evaluated by transmission electron microscopy and atomic absorption spectroscopy. Radioenhancing effect was assessed using conventional clonogenic assay.

RESULTS & CONCLUSION: Ctxb-AuNPs specifically bound to and accumulated in EGFR-overexpressing A431 cells, compared with EGFR-negative MDA-MB-453 cells. Ctxb-AuNPs enhanced the effect of proton irradiation in A431 cells but not in MDA-MB-453 cells. These data indicate, for the first time, that combining enhanced uptake by specific targeting and radioenhancing effect, using conjugated AuNPs, is a promising strategy to increase cell killing by protontherapy.

摘要

目的

本研究旨在开发抗体功能化金纳米粒子（AuNPs），以选择性靶向癌细胞，并在质子照射下探测其潜在的放射增敏作用。

材料与方法

AuNPs 与西妥昔单抗（Ctxb-AuNPs）偶联。通过透射电子显微镜和原子吸收光谱评估 Ctxb-AuNP 的摄取。采用常规集落形成实验评估放射增敏作用。

结果与结论

与 EGFR 阴性 MDA-MB-453 细胞相比，Ctxb-AuNPs 特异性结合并在 EGFR 过表达的 A431 细胞中积累。Ctxb-AuNPs 增强了 A431 细胞中质子照射的效果，但对 MDA-MB-453 细胞没有作用。这些数据首次表明，通过特异性靶向增强摄取和利用共轭 AuNPs 的放射增敏作用，是增加质子治疗细胞杀伤的一种有前途的策略。