Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer cells.
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.
Farokhzad
Omid C
OC
Department of Anesthesiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jon
Sangyong
S
Khademhosseini
Ali
A
Tran
Thanh-Nga T
TN
Lavan
David A
DA
Langer
Robert
R
D000954:Antigens, Surface / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000954:Antigens, Surface; D009841:Oligonucleotides; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II