Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology. Using
prostate cancer as a model, we report
docetaxel (Dtxl)-encapsulated nanoparticles formulated with biocompatible and biodegradable
poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) (
PLGA-b-PEG) copolymer and surface functionalized with the
A10 2'-fluoropyrimidine
RNA aptamers that recognize the extracellular domain of the prostate-specific membrane
antigen (PSMA), a well characterized
antigen expressed on the surface of
prostate cancer cells. These Dtxl-encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-
Apt) bind to the PSMA
protein expressed on the surface of LNCaP prostate epithelial cells and get taken up by these cells resulting in significantly enhanced in vitro cellular toxicity as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP) (P < 0.0004). The Dtxl-NP-
Apt bioconjugates also exhibit remarkable efficacy and reduced toxicity as measured by mean
body weight loss (BWL) in vivo [
body weight loss of 7.7 +/- 4% vs. 18 +/- 5% for Dtxl-NP-
Apt vs. Dtxl-NP at nadir, respectively (mean +/- SD); n = 7]. After a single intratumoral injection of Dtxl-NP-
Apt bioconjugates, complete
tumor reduction was observed in five of seven LNCaP xenograft nude mice (initial
tumor volume of approximately 300 mm3), and 100% of these animals survived our 109-day study. In contrast, two of seven mice in the Dtxl-NP group had complete
tumor reduction with 109-day survivability of only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles without drug were similarly nonefficacious. This report demonstrates the potential utility of nanoparticle-aptamer bioconjugates for a therapeutic application.