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

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Nano Research 2017年第7期10卷 2431-2448页

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

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

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Integrin-targeting with peptide-bioconjugated semiconductor-magnetic nanocrystalline heterostructures

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Nano Research 2016年第3期9卷 644-662页

作者： gianpiero valente Nicoletta Depalo Ivan de Paola Rosa Maria lacobazzi Nunzio Denora Valentino Laquintana Roberto Comparelli Emiliano Altamura Tiziana Latronico Michele Altomare Elisabetta Fanizza Marinella Striccoli Angela Agostiano Michele Saviano Annarita Del Gatto Laura Zaccaro Maria Lucia Curri Universita degli Studi di Bari Aldo Moro Dipartimento di Chimica Via Orabona 4 70125 - Bari Italy Istituto per i Processi Chimico-Fisici-CNR UOS Bari Via Orabona 4 70125 - Bari Italy Istituto di Biostrutture e Bioimmagini-CNR Via Mezzocannone 16 80134 - Napoli Italy Universita degli Studi di Bari Aldo Moro Dipartimento di Farmacia - Scienze del Farmaco Via Orabona 4 70125 - Bari Italy Universita degli Studi di BariAIdo Moro Dipartimento di Bioscienze Biotecnologie e Biofarmaceutica Via Orabona 4 70125 - Bari Italy lstituto di Cristallografia-CNR Via Amendola 122/0 70126 Bari Italy

Binary asymmetric nanocrystals （BNCs）, composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.

关键词： nanocrystallineheterostructures,photoactive semiconductor,magnetic nanostructure,cyclic RGD peptide,αvβ3 integrin,active targeting

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