title: Enhanced growth inhibition of prostate cancer in vitro and in vivo by a recombinant adenovirus-mediated dual-aptamer modified drug delivery system.
abstract: The peptide aptamer DUP-1 targets prostate-specific membrane antigen (PSMA)-negative cells, while the RNA aptamer A10-3.2 targets PSMA-positive prostate cancer cells. Moreover, the tumor-suppressor gene phosphatase and tensin homolog (PTEN) and the chemotherapeutic agent doxorubicin (DOX) effectively inhibit prostate cancer, and a recombinant adenovirus (Ad5) mediates high gene transfer efficiency. Here, we design a dual-aptamer modified tumor targeting gene and DOX delivery system mediated by recombinant adenovirus (A10-3.2(DOX)/DUP-1-PEG-Ad5, ADDP-Ad5). DUP-1 and A10-3.2 are connected to the adenovirus through polyethylene glycol (PEG), PTEN is integrated into Ad5, and DOX is embedded into the double chain of aptamer A10-3.2. The PEG-modification rate of Ad5 is 98.70 ± 2.43%. The DUP-1 and A10-3.2 modified products yield 80.40 ± 1.36% and 82.20 ± 2.14%, respectively. The uptake of ADDP-Ad5 and the expression of the reporter gene are enhanced by the system in PSMA-positive LNCaP and PSMA-negative PC3 human prostate cancer cells. ADDP-Ad5 significantly inhibits the cell growth of both LNCaP and PC3 cells. More importantly, ADDP-Ad5 is active in vivo against LNCaP and PC3 tumor xenografts and exhibits no significant toxicity to the mice. Therefore, ADDP-Ad5 may have clinical potential in prostate cancer therapy.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China; The Eighth Hospital of Xi'an, Xi'an, Shanxi 710061, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Jing
authors.affiliation: Laboratory of Cancer Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Shousong
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Shuangli
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Luzhou Senior High School, Luzhou, Sichuan 646000, China.
authors.forename: Siyun
authors.initials: S
authors.lastname: Ke
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Famin
authors.initials: F
authors.lastname: Ke
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Shurong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address: zhongzhirong@126.com.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000633:toxicity; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism*; D052158:Aptamers, Peptide / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D052158:Aptamers, Peptide; C501462:DUP-1 peptide; D010455:Peptides; D004317:Doxorubicin; D051059:PTEN Phosphohydrolase
keywords: Antitumor activity and toxicity; Doxorubicin; Dual aptamer; Recombinant adenovirus; Targeted drug delivery system