Nucleic acid ligands (aptamers) are potentially well suited for the therapeutic targeting of drug encapsulated controlled release
polymer particles in a cell- or tissue-specific manner. We synthesized a bioconjugate composed of controlled release
polymer nanoparticles and aptamers and examined its efficacy for targeted delivery to
prostate cancer cells. Specifically, we synthesized
poly(lactic acid)-block-
polyethylene glycol (PEG) copolymer with a terminal
carboxylic acid functional group (PLA-PEG-COOH), and encapsulated
rhodamine-labeled
dextran (as a model drug) within PLA-PEG-COOH nanoparticles. These nanoparticles have the following desirable characteristics: (a) negative surface charge (-50 +/- 3 mV, mean +/- SD, n = 3), which may minimize nonspecific interaction with the negatively charged
nucleic acid aptamers; (b)
carboxylic acid groups on the particle surface for potential modification and covalent conjugation to
amine-modified aptamers; and (c) presence of PEG on particle surface, which enhances circulating half-life while contributing to decreased uptake in nontargeted cells. Next, we generated nanoparticle-aptamer bioconjugates with
RNA aptamers that bind to the prostate-specific membrane
antigen, a well-known
prostate cancer tumor marker that is overexpressed on prostate acinar epithelial cells. We demonstrated that these bioconjugates can efficiently target and get taken up by the prostate LNCaP epithelial cells, which express the prostate-specific membrane
antigen protein (77-fold increase in binding versus control, n = 150 cells per group). In contrast to LNCaP cells, the uptake of these particles is not enhanced in cells that do not express the prostate-specific membrane
antigen protein. To our knowledge, this represents the first report of targeted drug delivery with nanoparticle-aptamer bioconjugates.