Abstract

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 PLAwith 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.

Original languageEnglish (US)
Pages (from-to)901-909
Number of pages9
JournalMicroscopy research and technique
Volume73
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • Cancer targeting
  • Cancer therapy
  • Chemotherapeutics
  • Conjugation
  • Cy5
  • Drug delivery
  • Fluorescence imaging
  • Nanomedicine
  • Polymeric nanoparticles
  • PSMA

ASJC Scopus subject areas

  • Anatomy
  • Instrumentation
  • Histology
  • Medical Laboratory Technology

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