Efficient delivery of micro RNA to bone-metastatic prostate tumors by using aptamer-conjugated atelocollagen in vitro and in vivo.
Bone is the primary site of skeletal metastasis in prostate cancer (PCa). Atelocollagen (ATE)-mediated siRNA delivery system can be used to silence endogenous genes involved in PCa metastatic tumor cell growth. However, we hope that the delivery system can target PCa cells to reduce damage to the bone tissue and improve the therapeutic effect. RNA aptamer (APT) A10-3.2 has been used as a ligand to target PCa cells that express prostate-specific membrane antigen (PSMA). APT was investigated as a PSMA-targeting ligand in the design of an ATE-based microRNA (miRNA; miR-15a and miR-16-1) vector to PCa bone metastasis. To observe the targeted delivery and transfection efficiency of ATE-APT in PSMA-overexpressing cells, luciferase activity and biodistribution of nanoparticles in Balb/c mice was analyzed. The anticancer effect of nanoparticles in vivo was investigated using the survival times of human PCa bone metastasis mice model. Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells showed that the transfection efficiency of the synthesized DNA/ATE-APT complex was higher than that of the DNA/ATE complex. The anticancer efficacy of miRNA/ATE-APT was superior to those of other treatments in vivo. This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of PCa cells in bone metastatic foci.
['Hao|Zhao|Z|', 'Fan|Wei|W|', 'Hao|Jian|J|', 'Wu|Xin|X|', 'Zeng|Guo Qing|GQ|', 'Zhang|Li Juan|LJ|', 'Nie|Sui Feng|SF|', 'Wang|Xu Dong|XD|']
D000818:Animals D052157:Aptamers, Nucleotide D001859:Bone Neoplasms D045744:Cell Line, Tumor D003094:Collagen D016503:Drug Delivery Systems D006801:Humans D008024:Ligands D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D035683:MicroRNAs D053758:Nanoparticles D011471:Prostatic Neoplasms D034741:RNA, Small Interfering D014018:Tissue Distribution D014162:Transfection
atelocollagen Aptamer prostate-specific membrane antigen miRNA targeted delivery prostate cancer metastasis