Ultrasound-Triggered Nanodroplets for Targeted Co-Delivery of Sorafenib/Doxorubicin for Hepatocellular Carcinoma Therapy.

The clinical treatment of hepatocellular carcinoma has been hindered due to the drug resistance and heterogeneity of tumor cells. A new therapy strategy combined chemo drugs and molecular-targeted drugs is considered to be promising for conquering these challenges. However, the different pharmacokinetic profiles, hydrophobicity and systemic toxicity of these drugs may still cause serious challenges to the clinical applications of this combination therapy. In this study, smart sorafenib (SF) and doxorubicin (DOX)-loaded nanodroplets (SF/DOX-NDs) were fabricated to solve the above issues. The liquid-to-gas phase transition of SF/DOX-NDs could function as a cavitation nucleus to boost drug release and increase cellular uptake after exposure to therapeutic ultrasound (TUS) irradiation. Additionally, this strategy has a therapeutic effect to induce apoptosis and inhibit the proliferation, migration, and invasion of hepatoma cells. Furthermore, the intense cavitation of SF/DOX-NDs at the tumor site could disrupt microvessels, which is beneficial for tissue-penetrating drug delivery inside tumors. Consequently, tumor angiogenesis was reduced, and tumor growth was remarkably inhibited by SF/DOX-NDs. These results indicated that combination therapy using SF/DOX-NDs may offer a promising approach to achieve effective HCC therapy with low side effects.

Preparation of sorafenib and doxorubicin loaded nanodroplets and its ultrasound-sensitive in vitro:experimental study / 中华超声影像学杂志

Objective To prepare ultrasound(US)responsive nanodroplets(NDs)simultaneously loaded with anticancer drug Sorafenib(SF)and Doxorubicin(DOX),and to characterize its ultrasound responsibility in vitro and in vivo.Methods The SF/DOX NDs were prepared using the thin-film hydration method.The particle diameter,Zeta potential and drug-encapsulation efficiency were characterized.The acoustic droplets vaporization activity was monitored by in vitro ultrasound imaging and light microscope. The cavitation effect was monitored by in vitro ultrasound imaging and transmission electron microscopy. Results SF/DOX NDs were round in shape,the mean diameter and Zeta potential of SF/DOX NDs was (498 ± 67.34)nm,-(38.87 ± 3.78)mV,respectively.The entrapment efficiency of SF and DOX was (58.14±2.93)%,(51.23±4.11)%,respectively.SF/DOX NDs underwent a phase transition into bubbles and could be continuously imaged for more than 25 min in vitro,and afterward therapeutic ultrasound pulse induced inertial cavitation and substantially enhanced treatment.Conclusions US-responsible SF/DOX NDs are prepared using thin-film hydration mehtod,it can enhance ultrasonic echo in vitro and release anticancer drug by the aid of US exposure,which possesses greater researching and applicating value.