Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy
Xin Wu1,*, Baoyue Ding1,2,*, Jing Gao3,*, Huanyun Wang4, Wei Fan1, Xiang Wang1,5, Wei Zhang1, Xiaoyu Wang1, Lihua Ye1, Min Zhang1, Xueying Ding3, Jiyong Liu1, Quangang Zhu1, Shen Gao1
1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai; 2Medical College of Jiaxing University, Jiaxing; 3School of Pharmacy, Second Military Medical University, Shanghai; 4School of Pharmacy, Inner Mongolia Medical College, Hohhot; 5No. 98 Hospital of PLA, Huzhou, People’s Republic of China
*These authors contributed equally to this work
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 IC50 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.
Keywords: miRNA, aptamer, polyamidoamine, prostate-specific membrane antigen, targeted delivery, prostate cancer
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