title: Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo.
abstract: Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer-modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa.
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China ; Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Tai
authors.affiliation: Department of Pharmaceutics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Quangang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, The 425th Hospital of PLA, Sanya, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People's Republic of China.
authors.forename: Baoyue
authors.initials: B
authors.lastname: Ding
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China ; Department of Pharmaceutics, The 522nd Hospital of PLA, Luoyang, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Gaolin
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001835:Body Weight / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011471:Prostatic Neoplasms / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D035683:MicroRNAs; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: aptamer; miRNA; polyamidoamine; prostate cancer; prostate-specific membrane antigen; targeted delivery