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Polylactide nanoparticles containing stably incorporated cyanine dyes for in vitro and in vivo imaging applications
Author(s) -
Tong Rong,
Coyle Virginia J.,
Tang Li,
Barger Anne M.,
Fan Timothy M.,
Cheng Jianjun
Publication year - 2010
Publication title -
microscopy research and technique
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 118
eISSN - 1097-0029
pISSN - 1059-910X
DOI - 10.1002/jemt.20824
Subject(s) - in vivo , cyanine , chemistry , conjugated system , in vitro , fluorescence , biophysics , aptamer , lncap , nanoparticle , micelle , covalent bond , carbodiimide , combinatorial chemistry , polymer , nanotechnology , biochemistry , cancer cell , materials science , organic chemistry , microbiology and biotechnology , cancer , aqueous solution , biology , physics , quantum mechanics , genetics
Stably incorporating fluorescent molecules to polymeric nanoparticles (NPs) or micelles can facilitate the prolonged tracking of these drug‐delivery vehicles in vitro and in vivo. However, incorporation of fluorescent molecules, usually charged and thereby water‐soluble, through the encapsulation strategy to hydrophobic polymer matrices is challenging. The encapsulated fluorescent agents are also subject to rapid release when the polymeric NPs are exposed to biological media. To address this issue, we developed Cy5‐conjugated polylactide (Cy5‐PLA) NPs through Cy5/(BDI)ZnN(TMS) 2 [(BDI) = 2‐((2,6‐diisopropylphenyl)amido)‐4‐((2,6‐diisopropylphenyl)‐imino)‐2‐pentene]‐mediated ring‐opening polymerization of lactide (LA) followed by nanoprecipitation. This process allows for covalent conjugation of Cy5 to PLA with quantitative incorporation efficiency and formulation of Cy5‐PLA NPs with controlled particles size (≈100 nm). As much as 80% of Cy5 was still present in the Cy5‐PLA NPs after theses NPs were incubated in PBS at 37°C for 12 days. Cy5‐PLA NPs were conjugated to the A10 RNA aptamer that binds to the prostate‐specific membrane antigen (PSMA). The resulting Cy5‐PLA/aptamer NPs were found to only bind to and get internalized by LNCaP and canine prostate adenocarcinoma cells (PSMA‐positive), but not to PC3 cells (PSMA‐negative). The Cy5‐PLA NPs were administered to balb/c mice intravenously and found to have excellent signals with low‐background fluorescence in various organs. Microsc. Res. Tech. 73:901–909, 2010. © 2010 Wiley‐Liss, Inc.