Khanna Vidhi, Kalscheuer Stephen, Kirtane Ameya, Zhang Wenqiu, Panyam Jayanth
Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Future Drug Discov. 2019 Jul 1;1(1):FDD8. doi: 10.4155/fdd-2019-0005. eCollection 2019 Jul.
We previously developed two antibodies that bind to a cell surface protein, perlecan, overexpressed in triple-negative breast cancer (TNBC). The goal of this study was to investigate these antibodies as targeting ligands for nanoparticle-mediated drug delivery.
Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles were functionalized with antibodies using thiol-maleimide chemistry. Effect of antibody functionalization on therapeutic efficacy of drug-loaded nanoparticles was investigated using and models of TNBC.
The antibodies were covalently conjugated to nanoparticles without affecting antibody binding affinity or nanoparticle properties. Perlecan-targeted nanoparticles showed improved cell uptake, retention, cytotoxicity and enhanced tumor growth inhibition .
The data presented here indicates that perlecan-targeted nanoparticles can improve tumor drug delivery to TNBC.
我们之前研发了两种抗体，它们可与一种在三阴性乳腺癌（TNBC）中过表达的细胞表面蛋白——基底膜聚糖结合。本研究的目的是研究这些抗体作为纳米颗粒介导的药物递送的靶向配体。
使用硫醇-马来酰亚胺化学方法，用抗体对负载紫杉醇的聚（D，L-丙交酯-共-乙交酯）纳米颗粒进行功能化修饰。使用TNBC的[具体模型1]和[具体模型2]模型研究抗体功能化对载药纳米颗粒治疗效果的影响。
抗体与纳米颗粒共价结合，且不影响抗体结合亲和力或纳米颗粒特性。靶向基底膜聚糖的纳米颗粒表现出改善的细胞摄取、滞留、细胞毒性[具体指标1]以及增强的肿瘤生长抑制[具体指标2]。
此处呈现的数据表明，靶向基底膜聚糖的纳米颗粒可改善对TNBC的肿瘤药物递送。
