Radiolabeled block copolymer micelles for image-guided drug delivery

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• 作者：Elisabete Ribeiro^a ; Irina Alho^b ; Fernanda Marques^a ; Lurdes Gano^a ; Isabel Correia^c ; Joã ; o D.G. Correia^a ; Sandra Casimiro^b ; Luí ; s Costa^b ; Isabel Santos^a ; Cé ; lia Fernandes^a ; ^{celiaf@ctn.tecnico.ulisboa.pt}
• 关键词：DTX ; docetaxel ; BCMs ; block copolymer micelles ; PEG ; poly(ethylene glycol) ; PCL ; poly(ε-caprolactone) ; PB ; phosphate buffer ; DLS ; dynamic light scattering ; TEM ; transmission electron microscopy ; CMC ; critical micelle concentration ; LC ; DTX loading content ; LE ; DTX loading efficiency
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 December 2016
• 年：2016
• 卷：515
• 期：1-2
• 页码：692-701
• 全文大小：1460 K
• 卷排序：515

文摘

We aimed at exploring block copolymer micelles (BCMs) for the simultaneous delivery of radiation/chemotherapy to cancer cells. To achieve that goal, we have prepared and characterized a novel type of docetaxel (DTX) loaded and non-loaded BCMs. The micelles were decorated with pyrazolyl-diamine chelating units to stabilize the matched pair 99mTc/Re for image-guided delivery of therapeutic drugs. The in vitro studies have shown that DTX release is pH-dependent increasing at lower pH values. Anti-proliferative studies in different cancer cell lines showed that DTX-loaded BCMs present relevant anti-proliferative activity. In comparison to free DTX, the loaded-micelles exhibited higher anti-proliferative activity for the same DTX concentration, which mean that a similar therapeutic outcome may be achieved with reduced side effects. The pyrazolyl-diamine-functionalized micelles were labeled with fac-[99mTc(CO)3(H2O)3]+ in high radiochemical yield and purity. The radiolabeled micelles are stable in phosphate buffer and in cell culture media. Cellular uptake studies in different cancer cell lines indicate a cell type and time-dependent uptake, in agreement with the anti-proliferative activity. Early biodistribution studies in healthy BALB/c mice has shown prolonged circulation lifetime in the bloodstream and relevant in vivo stability, important features when considering an effective DTX delivery system and image-guided delivery agent for cancer theranostics.