title: Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy.
abstract: BACKGROUND
  miR-15a and miR-16-1 have been identified as tumor suppressor genes in prostate cancer, but their safe and effective delivery to target cells is key to the successful use of this therapeutic strategy. RNA aptamer A10 has been used as a ligand, targeting prostate cancer cells that express prostate-specific membrane antigen (PSMA). Compared with A10, the binding of the second-generation RNA aptamer, A10-3.2, to PSMA is more efficient.
  
  
  METHODS
  A10-3.2 was investigated as a PSMA-targeting ligand in the design of a polyamidoamine (PAMAM)-based microRNA (miR-15a and miR-16-1) vector to prostate cancer cells. Using polyethyleneglycol (PEG) as a spacer, PAMAM was conjugated to aptamer (PAMAM-PEG-APT) and used as a vehicle for miRNA target delivery.
  
  
  RESULTS
  Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells demonstrated that the transfection efficiency of the synthesized DNA/PAMAM-PEG-APT complex was higher than that of the DNA/PAMAM-PEG complex. In addition, cell viability assays of LNCaP (PSMA(+)) cells showed that, with a N/P ratio of 15:1, the IC(50) value of miRNA/PAMAM-PEG-APT was approximately 4.7-fold lower than that of miRNA/PAMAM-PEG.
  
  
  CONCLUSIONS
  This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of prostate cancer cells.
authors: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China.
authors: Xin
authors: X
authors: Wu
authors: Baoyue
authors: B
authors: Ding
authors: Jing
authors: J
authors: Gao
authors: Huanyun
authors: H
authors: Wang
authors: Wei
authors: W
authors: Fan
authors: Xiang
authors: X
authors: Wang
authors: Wei
authors: W
authors: Zhang
authors: Xiaoyu
authors: X
authors: Wang
authors: Lihua
authors: L
authors: Ye
authors: Min
authors: M
authors: Zhang
authors: Xueying
authors: X
authors: Ding
authors: Jiyong
authors: J
authors: Liu
authors: Quangang
authors: Q
authors: Zhu
authors: Shen
authors: S
authors: Gao
mesh_terms: D000704:Analysis of Variance; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D035683:MicroRNAs / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011073:Polyamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014162:Transfection
chemical_list: D000954:Antigens, Surface; D052157:Aptamers, Nucleotide; D035683:MicroRNAs; C531249:Poly(amidoamine); D011073:Polyamines; D011092:Polyethylene Glycols; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II