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 ...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.展开更多
文摘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.
