PURPOSE: Both combretastatin A-4 (CA-4) and doxorubicin (DOX) was loaded in different form in a targeted nanomedicine in order to achieve the active delivery of these two drugs followed by sequentially suppressing tumor vasculature and tumor cells. METHODS: Octreotide-modified stealth liposomes loaded with CA-4 and DOX (Oct-L[CD]) were prepared and characterized. Then in vitro release, cellular uptake, in vitro antitumor effect, pharmacokinetics, in vivo sequential killing effect, in vivo antitumor efficacy against somatostatin receptor (SSTR) positive cells, as well as the action mechanism of such system, were studied. RESULTS: A rapid release of CA-4 followed by a slow release of DOX was observed in vitro. The active targeted liposomes Oct-L[CD] showed a specific cellular uptake through ligand-receptor interaction and a higher antitumor effect in vitro against SSTR-positive cell line. The in vivo sequential killing effect of such system was found as evidenced by the fast inhibition of blood vessels and slow apoptosis-inducing of tumor cells. Oct-L[CD] also exhibited the strongest antitumor effect in MCF-7 subcutaneous xenograft models. CONCLUSIONS: Oct-modified co-delivery system may have great potential as an effective carrier for cancer therapy.
PURPOSE: Both combretastatin A-4 (CA-4) and doxorubicin (DOX) was loaded in different form in a targeted nanomedicine in order to achieve the active delivery of these two drugs followed by sequentially suppressing tumor vasculature and tumor cells. METHODS:Octreotide-modified stealth liposomes loaded with CA-4 and DOX (Oct-L[CD]) were prepared and characterized. Then in vitro release, cellular uptake, in vitro antitumor effect, pharmacokinetics, in vivo sequential killing effect, in vivo antitumor efficacy against somatostatin receptor (SSTR) positive cells, as well as the action mechanism of such system, were studied. RESULTS: A rapid release of CA-4 followed by a slow release of DOX was observed in vitro. The active targeted liposomes Oct-L[CD] showed a specific cellular uptake through ligand-receptor interaction and a higher antitumor effect in vitro against SSTR-positive cell line. The in vivo sequential killing effect of such system was found as evidenced by the fast inhibition of blood vessels and slow apoptosis-inducing of tumor cells. Oct-L[CD] also exhibited the strongest antitumor effect in MCF-7 subcutaneous xenograft models. CONCLUSIONS: Oct-modified co-delivery system may have great potential as an effective carrier for cancer therapy.
Authors: Siow Ming Lee; Penella J Woll; Robin Rudd; David Ferry; Mary O'Brien; Gary Middleton; Stephen Spiro; Lindsay James; Kulsam Ali; Mark Jitlal; Allan Hackshaw Journal: J Natl Cancer Inst Date: 2009-07-16 Impact factor: 13.506
Authors: Damian Wild; Jörg S Schmitt; Mihaela Ginj; Helmut R Mäcke; Bert F Bernard; Eric Krenning; Marion De Jong; Sandra Wenger; Jean-Claude Reubi Journal: Eur J Nucl Med Mol Imaging Date: 2003-08-21 Impact factor: 9.236
Authors: Stephen W Morton; Michael J Lee; Zhou J Deng; Erik C Dreaden; Elise Siouve; Kevin E Shopsowitz; Nisarg J Shah; Michael B Yaffe; Paula T Hammond Journal: Sci Signal Date: 2014-05-13 Impact factor: 8.192