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.

CONCLUSION:

This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of prostate cancer cells.

• Authors: Xin Wu, Baoyue Ding, Jing Gao, Huanyun Wang, Wei Fan, Xiang Wang, Wei Zhang, Xiaoyu Wang, Lihua Ye, Min Zhang, Xueying Ding, Jiyong Liu, Quangang Zhu, Shen Gao
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 6 Pg. 1747-56 ( 2011) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 21980237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• Aptamers, Nucleotide
• MicroRNAs
• Poly(amidoamine)
• Polyamines
• Polyethylene Glycols
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Analysis of Variance
• Antigens, Surface (genetics, metabolism)
• Aptamers, Nucleotide (administration & dosage, chemistry, genetics, metabolism)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Delivery Systems (methods)
• Flow Cytometry
• Gene Expression (drug effects)
• Glutamate Carboxypeptidase II (genetics, metabolism)
• Humans
• Magnetic Resonance Spectroscopy
• Male
• MicroRNAs (administration & dosage, chemistry, genetics, metabolism)
• Microscopy, Fluorescence
• Polyamines (chemistry)
• Polyethylene Glycols (chemistry)
• Prostatic Neoplasms (genetics, metabolism, pathology, therapy)
• Transfection