caa a22 4500 445313846 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-011-0381-1 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0381-1 Octreotide-Modified Polymeric Micelles as Potential Carriers for Targeted Docetaxel Delivery to Somatostatin Receptor Overexpressing Tumor Cells [Elektronische Daten] [Yuan Zhang, Xueqing Wang, Jiancheng Wang, Xuan Zhang, Qiang Zhang] ABSTRACT: Purpose: Somatostatin analogue octreotide (OCT)-modified PEG-b-PLA micelles were constructed to bind to somatostatin receptors (SSTRs) overexpressed on tumor cells for enhanced intracellular drug delivery and improved therapeutic efficacy for malignant tumors. Methods: Copolymers conjugated with octreotide (OCT-PEG6000-b-PLA5000) were synthesized. The fluorescent probe DiI or docetaxel (DTX)-loaded micelles with or without octreotide modification (OCT-PM-DiI, PM-DiI, OCT-PM-DTX and PM-DTX) were prepared, and their physiochemical properties, intracellular delivery in vitro or anti-tumor activity in vivo were evaluated, respectively. Results: The CMC of OCT-PEG6000-b-PLA5000 was quite low (<10−6mol/L). All micelles were less than 80nm with spherical shape and high encapsulation efficiency. DTX molecules were well dispersed in the micelles without chemical interactions with the polymers. Flow cytometry and confocal microscopy results showed that OCT-PM-DiI enhanced intracellular delivery efficiency via receptor-mediated endocytosis in NCI-H446 cells; the optimal modification ratio of OCT on micelle surface was 5%. OCT-PM-DTX exhibited higher retardation of tumor growth after intravenous injections into xenograft NCI-H446 tumor model; octreotide-modified micelles did not show severe toxicity. Conclusions: SSTRs targeting micelles may serve as promising nanocarriers in tumor treatment for hydrophobic anticancer drugs, such as DTX. Springer Science+Business Media, LLC, 2011 antitumor efficacy nationallicence DTX nationallicence intracellular delivery nationallicence octreotide nationallicence polymeric micelles nationallicence Zhang Yuan State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut Wang Xueqing State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut Wang Jiancheng State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut Zhang Xuan State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut Zhang Qiang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1167-1178 0724-8741 28:5<1167 2011 28 11095 https://doi.org/10.1007/s11095-011-0381-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0381-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Yuan State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wang Xueqing State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wang Jiancheng State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Xuan State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Qiang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, 100191, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1167-1178 0724-8741 28:5<1167 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer