Sorafenib delivery nanoplatform based on superpara- magnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma  

作　　者：Nicoletta Depalo Rosa Maria lacobazzi Gianpiero Valente Ilaria Arduino Silvia Villa Fabio Canepa Valentino Laquintana Elisabetta Fanizza Marinella Striccoli Annalisa Cutrignelli Angela Lopedota Letizia Porcelli Amalia Azzariti Massimo Franco Maria Lucia Curri Nunzio Denora 

机构地区：[1]Istituto per i Processi Chimico-Fisici-CNR UOS Bari, Via Orabona 4, 70125 Bari, Italy [2]Istituto Tumori IRCCS Giovanni Paolo II, viale O. Flacco 65, 70124 Bari, Italy [3]Dipartimento di Chimica, Universita degli Studi di Bad Aldo Moro, Via Orabona70125 Bari, Italy [4]Dipartimento di Farmacia-Scienze del Farmaco, Universita degli Studi di Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy [5]Dipartimento di Chimica e Chimica Industriale, Universita di Genova, Via Dodecaneso 31, 16146 Genova, Italy

出　　处：《Nano Research》2017年第7期2431-2448,共18页纳米研究（英文版）

摘　　要：Currently, sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients. Unfortunately, its side effects, particularly its overall toxicity, limit the therapeutic response that can be achieved. Superparamagnetic iron oxide nanoparticles （SPIONs） are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field, thus improving intratumoral accumulation and reducing adverse effects. Here, nanoformulations based on polyethylene glycol modified phospholipid micelles, loaded with both SPIONs and sorafenib, were successfully prepared and thoroughly investigated by complementary techniques. This nanovector system provided effective drug delivery, had an average hydrodynamic diameter of about 125 nm, had good stability in aqueous medium, and allowed controlled drug loading. Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle. An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver. Human hepatocellular carcinoma （HepG2） cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib. These experiments demonstrated that this delivery platform is able to enhance sorafenib＇s antitumor effectiveness by magnetic targeting. The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites, where selective release of sorafenib can improve its efficacy and safety profile.Currently, sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients. Unfortunately, its side effects, particularly its overall toxicity, limit the therapeutic response that can be achieved. Superparamagnetic iron oxide nanoparticles （SPIONs） are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field, thus improving intratumoral accumulation and reducing adverse effects. Here, nanoformulations based on polyethylene glycol modified phospholipid micelles, loaded with both SPIONs and sorafenib, were successfully prepared and thoroughly investigated by complementary techniques. This nanovector system provided effective drug delivery, had an average hydrodynamic diameter of about 125 nm, had good stability in aqueous medium, and allowed controlled drug loading. Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle. An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver. Human hepatocellular carcinoma （HepG2） cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib. These experiments demonstrated that this delivery platform is able to enhance sorafenib＇s antitumor effectiveness by magnetic targeting. The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites, where selective release of sorafenib can improve its efficacy and safety profile.

关 键 词：superparamagnetic ironoxide nanoparticles poly（ethylene glycol） （PEG）-modified phospholipidmicelles drug delivery magnetic targeting hepatocellular carcinoma SORAFENIB 

分 类 号：Q789[生物学—分子生物学] TQ110[化学工程—无机化工]