Radiolabeled block copolymer micelles for image-guided drug delivery.
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 pair99mTc/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.
Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
Elisabete
E
Ribeiro
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Irina
I
Alho
Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
Fernanda
F
Marques
Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
Lurdes
L
Gano
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Isabel
I
Correia
Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
João D G
JDG
Correia
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Sandra
S
Casimiro
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Luís
L
Costa
Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
Isabel
I
Santos
Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal. Electronic address: celiaf@ctn.tecnico.ulisboa.pt.
Célia
C
Fernandes
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D011868:Radioisotopes; D043823:Taxoids; D000077143:Docetaxel
(99m)Tc; Block copolymer micelle; Drug delivery system; PEG-b-PCL; Radiolabeled micelles