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.
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Dual aptamer (A10-3.2 and DUP-1) delivery system enhances drug uptake and gene expression in prostate cancer cells.
“Jing et al. also prepared a dual aptamer modified (the second-generation RNA aptamer A10-3.2 and DUP-1) delivery system to deliver tumor suppressor genes and doxorubicin. This system enhances drug uptake and gene expression in prostate cancer cells.249”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [249]
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Smart nanoparticles for cancer therapy
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- Authors
- Jing, P., Cao, S., Xiao, S., Zhang, X., Ke, S., Ke, F., Yu, X., Wang, L., Wang, S., Luo, Y., & Zhong, Z.
- Affiliations
- Southwest Medical University (CN)
- Corresponding author
- Zhong, Zhirong
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 383
- Issue
- 2
- Pages
- 230-242
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2528546669
- Cited by
- 37
- References
- 36
- Citations by year
- 2025: 4 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 6
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81202479)
- Major Cultivation Item of Educational Department of Sichuan Province (14CZ0018)
- Collaborative Fund of Science and Technology Agency of Sichuan Province, Luzhou Government and Southwest Medical University (2014JC0126, 2014JC0800)
- Collaborative Fund of Luzhou Government and Southwest Medical University (2013LZLY-J54)
- Southwest Medical University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- prostate cancer, adenoviral vector, peptide aptamers, RNA aptamers, prostate-specific membrane antigen, PTEN, doxorubicin, gene delivery, PEGylation, tumor targeting, LNCaP cells, PC-3 cells, tumor xenografts, cancer therapy
- MeSH terms
- Adenoviridae, Animals, Antibiotics, Antineoplastic, Doxorubicin, Genetic Vectors, Humans, Male, Mice, Nude, Peptides, Prostatic Neoplasms, Time Factors, Transfection, Genetic Therapy, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Drug Delivery Systems, Xenograft Model Antitumor Assays, Tumor Burden, Cell Proliferation, PTEN Phosphohydrolase, Aptamers, Nucleotide, Aptamers, Peptide, Hep G2 Cells, HEK293 Cells
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