title: Efficient delivery of micro RNA to bone-metastatic prostate tumors by using aptamer-conjugated atelocollagen in vitro and in vivo.
abstract: 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.
authors.affiliation: a Department of Orthopedics , The 425th Hospital of PLA , Sanya , China .
authors.forename: Zhao
authors.initials: Z
authors.lastname: Hao
authors.affiliation: b Department of Pharmacy , The 425th Hospital of PLA , Sanya , China .
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: c Department of Orthopedics , Nankai Hospital , Tianjin , China , and.
authors.forename: Jian
authors.initials: J
authors.lastname: Hao
authors.affiliation: d Department of Pharmacy , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: b Department of Pharmacy , The 425th Hospital of PLA , Sanya , China .
authors.forename: Guo Qing
authors.initials: GQ
authors.lastname: Zeng
authors.affiliation: d Department of Pharmacy , Changhai Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: a Department of Orthopedics , The 425th Hospital of PLA , Sanya , China .
authors.forename: Sui Feng
authors.initials: SF
authors.lastname: Nie
authors.affiliation: b Department of Pharmacy , The 425th Hospital of PLA , Sanya , China .
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003094:Collagen / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000008:administration & dosage*; D053758:Nanoparticles / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D014018:Tissue Distribution / Q000187:drug effects; D014162:Transfection / Q000379:methods
chemical_list: D052157:Aptamers, Nucleotide; D008024:Ligands; D035683:MicroRNAs; D034741:RNA, Small Interfering; C059821:atelocollagen; D003094:Collagen
keywords: Aptamer; atelocollagen; miRNA; prostate cancer metastasis; prostate-specific membrane antigen; targeted delivery