Vishwasrao Hemant M, Master Alyssa M, Seo Youn Gee, Liu Xinming M, Pothayee Nikorn, Zhou Zhengyuan, Yuan Dongfen, Boska Michael D, Bronich Tatiana K, Davis Richey M, Riffle Judy S, Sokolsky-Papkov Marina, Kabanov Alexander V
Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
Center for Nanotechnology in Drug Delivery, Molecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Chem Mater. 2016 May 10;28(9):3024-3040. doi: 10.1021/acs.chemmater.6b00197. Epub 2016 May 2.
Given the superior soft tissue contrasts obtained by MRI and the long residence times of magnetic nanoparticles (MNPs) in soft tissues, MNP-based theranostic systems are being developed for simultaneous imaging and treatment. However, development of such theranostic nanoformulations presents significant challenges of balancing the therapeutic and diagnostic functionalities in order to achieve optimum effect from both. Here we developed a simple theranostic nanoformulation based on magnetic nanoclusters (MNCs) stabilized by a bisphosphonate-modified poly(glutamic acid)--(ethylene glycol) block copolymer and complexed with cisplatin. The MNCs were decorated with luteinizing hormone releasing hormone (LHRH) to target LHRH receptors (LHRHr) overexpressed in ovarian cancer cells. The targeted MNCs significantly improved the uptake of the drug in cancer cells and decreased its IC compared to the nontargeted formulations. Also, the enhanced LHRHr-mediated uptake of the targeted MNCs resulted in enhancement in the T-weighted negative contrast in cellular phantom gels. Taken together, the LHRH-conjugated MNCs show good potential as ovarian cancer theranostics.
鉴于磁共振成像（MRI）能获得出色的软组织对比度，以及磁性纳米颗粒（MNPs）在软组织中的长时间滞留，基于MNP的诊疗系统正在被开发用于同时成像和治疗。然而，开发这种诊疗纳米制剂面临着重大挑战，即要平衡治疗和诊断功能，以便从两者中获得最佳效果。在此，我们开发了一种简单的诊疗纳米制剂，它基于由双膦酸盐修饰的聚（谷氨酸）-（乙二醇）嵌段共聚物稳定并与顺铂络合的磁性纳米簇（MNCs）。MNCs用促黄体激素释放激素（LHRH）进行修饰，以靶向在卵巢癌细胞中过表达的LHRH受体（LHRHr）。与非靶向制剂相比，靶向MNCs显著提高了癌细胞对药物的摄取并降低了其半数抑制浓度（IC）。此外，靶向MNCs通过增强LHRHr介导的摄取，导致细胞模型凝胶中T2加权负对比度增强。综上所述，LHRH偶联的MNCs作为卵巢癌诊疗剂具有良好的潜力。
