期刊
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
卷 26, 期 6, 页码 634-646出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10837450.2021.1912090
关键词
Doxorubicin; siRNA; nanobubbles; NGR; CPP
NGR-modified nanobubbles containing CPP-DOX and CPP-siRNA demonstrate stable and controlled release of doxorubicin and siRNA, enhanced drug accumulation in tumors with sonication, and potential application prospects in cancer therapy.
A combination of doxorubicin (DOX) and small interfering RNA (siRNA) is proven effective for the reverse of multidrug resistance. However, rapid degradation and poor cellular internalization of siRNA hinder their synergistic action. To improve the combination effect, asparagine-glycine-arginine peptide (NGR) -modified nanobubbles (NBs) containing cell-penetrating peptide (CPP) decorated DOX and CPP decorated c-myc siRNA were constructed. Diameters of these NBs were about 245 nm and zeta potentials were about -3 mV. Encapsulation efficiencies (EE) of DOX exceeded 80%. Release of DOX could be triggered by ultrasound (US) since above 80% DOX was released from NBs after sonication while less than 5% DOX was discharged without treatment of US. These NBs were considered stable during 24 h since the decrease of particle size was no more than 10 nm, variances of EE were less than 5%, and changes of transmission (Delta T) were less than 3%. More drugs in formulation decorated with CPP and NGR were accumulated in the tumor when combined with sonication. The evident synergistic action of DOX, siRNA, NBs, and US was verified in mice with strong antitumor efficacy. Taken together, NGR-modified NBs containing CPP-DOX and CPP-siRNA are able to realize time- and spatial-controlled drug delivery and show potential application prospects.
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