Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy.
Presented study aimed to prepare A10 aptamer-modified poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with triplex forming oligonucleotides(TFO) for targeted prostate cancer therapy. We first synthesized a PLGA-PEG-Apt copolymer. The PLGA-PEG-Apt nanoparticles (NP-Apt) were loaded with TFO using double emulsion solvent evaporation method. Carboxy-fluorescein labeled TFO-NP-Apt, TFO-NP and TFO were prepared for cellular uptake experiments. Cell counting kit-8 (CCK-8) test was used to determine the ability of TFO-NP-Apt to inhibit LNCaP cell proliferation. RT-PCR and Western blot was conducted to analyze AR gene expressing. Then, a mouse model of prostate cancer was used to evaluate the anti-cancer effect of TFO-NP-Apt in vivo. We confirmed that the PLGA-PEG-Apt conjugation was successful. The TFO encapsulation efficiency and drug loading percentage were 46.1± 3.6% and 40.8±5.3%, respectively. TFO-NP-Apt showed a more efficient cellular uptake than TFO-NP or TFO in LNCaP cells. TFO-NP-Apt was significantly more cytotoxic than TFO-NP and TFO in the CCK-8 test (p<0.001). TFO-NP-Apt silenced the AR gene better than unconjugated Apt, naked TFO, NP or saline. TFO-NP-Apt were more effective than TFO-NP, naked TFO, NP and saline at inhibiting prostate cancer growth in vivo (p<0.05). Aptamer-modified TFO-loaded PLGA nanoparticles may prove useful in targeted therapy for advanced prostate cancer.
J
J
Jiao
Q
Q
Zou
M H
MH
Zou
R M
RM
Guo
S
S
Zhu
Y
Y
Zhang
D000818:Animals; D052157:Aptamers, Nucleotide / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D036103:Nanotechnology / Q000379:methods; D009841:Oligonucleotides / Q000627:therapeutic use*; D011091:Polyesters; D011092:Polyethylene Glycols; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D019344:Lactic Acid; D011092:Polyethylene Glycols
aptamer; prostate cancer.; prostate-specific membrane antigen; triplex forming oligonucleotide