Department of Materials Science and Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison , 330 N. Orchard Street, Madison, Wisconsin 53715, United States.
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53706, United States.
ACS Appl Mater Interfaces. 2017 Sep 13;9(36):30297-30305. doi: 10.1021/acsami.7b05654. Epub 2017 Aug 28.
A quantum-dot (QD)-based micelle conjugated with an anti-epidermal growth factor receptor (EGFR) nanobody (Nb) and loaded with an anticancer drug, aminoflavone (AF), has been engineered for EGFR-overexpressing cancer theranostics. The near-infrared (NIR) fluorescence of the indium phosphate core/zinc sulfide shell QDs (InP/ZnS QDs) allowed for in vivo nanoparticle biodistribution studies. The anti-EGFR nanobody 7D12 conjugation improved the cellular uptake and cytotoxicity of the QD-based micelles in EGFR-overexpressing MDA-MB-468 triple-negative breast cancer (TNBC) cells. In comparison with the AF-encapsulated nontargeted (i.e., without Nb conjugation) micelles, the AF-encapsulated Nb-conjugated (i.e., targeted) micelles accumulated in tumors at higher concentrations, leading to more effective tumor regression in an orthotopic triple-negative breast cancer xenograft mouse model. Furthermore, there was no systemic toxicity observed with the treatments. Thus, this QD-based Nb-conjugated micelle may serve as an effective theranostic nanoplatform for EGFR-overexpressing cancers such as TNBCs.
一种基于量子点（QD）的胶束与一种抗表皮生长因子受体（EGFR）纳米抗体（Nb）偶联，并负载抗癌药物氨基黄酮（AF），已被设计用于 EGFR 过表达癌症的治疗诊断。近红外（NIR）荧光的磷化铟核/硫化锌壳 QD（InP/ZnS QD）允许进行体内纳米颗粒生物分布研究。抗 EGFR 纳米抗体 7D12 的偶联提高了 QD 基胶束在 EGFR 过表达 MDA-MB-468 三阴性乳腺癌（TNBC）细胞中的细胞摄取和细胞毒性。与包封 AF 的非靶向（即，无 Nb 偶联）胶束相比，包封 AF 的 Nb 偶联（即靶向）胶束在肿瘤中以更高的浓度积累，导致在原位三阴性乳腺癌异种移植小鼠模型中更有效的肿瘤消退。此外，治疗中没有观察到全身毒性。因此，这种基于 QD 的 Nb 偶联胶束可作为 EGFR 过表达癌症（如 TNBC）的有效治疗诊断纳米平台。
