Spatiotemporally controlled co-delivery of anti-vasculature agent and cytotoxic drug by octreotide-modified stealth liposomes.
OBJECTIVE
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.
State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
Wenbing
W
Dai
Wu
W
Jin
Junlin
J
Zhang
Xueqing
X
Wang
Jiancheng
J
Wang
Xuan
X
Zhang
You
Y
Wan
Qiang
Q
Zhang
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D008024:Ligands; D008081:Liposomes / Q000008:administration & dosage*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015282:Octreotide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D008024:Ligands; D008081:Liposomes; D017481:Receptors, Somatostatin; D013267:Stilbenes; D004317:Doxorubicin; C058728:fosbretabulin; D015282:Octreotide