Oncolytic Adenovirus Coated with Multidegradable Bioreducible Core-Cross-Linked Polyethylenimine for Cancer Gene Therapy - PubMed (original) (raw)
. 2015 Jul 13;16(7):2132-43.
doi: 10.1021/acs.biomac.5b00538. Epub 2015 Jun 29.
Affiliations
- PMID: 26096567
- DOI: 10.1021/acs.biomac.5b00538
Oncolytic Adenovirus Coated with Multidegradable Bioreducible Core-Cross-Linked Polyethylenimine for Cancer Gene Therapy
Joung-Woo Choi et al. Biomacromolecules. 2015.
Abstract
Recently, adenovirus (Ad) has been utilized as a viral vector for efficient gene delivery. However, substantial immunogenicity and toxicity have obstructed oncolytic Ad's transition into clinical studies. The goal of this study is to generate an adenoviral vector complexed with multidegradable bioreducible core-cross-linked polyethylenimine (rPEI) polymer that has low immunogenicity and toxicity while having higher transduction efficacy and stability. We have synthesized different molecular weight rPEIs and complexed with Ad at varying molar ratios to optimize delivery of the Ad/polymer complex. The size and surface charge of Ad/rPEIs were characterized. Of note, Ad/rPEIs showed significantly enhanced transduction efficiency compared to either naked Ad or Ad/25 kDa PEI in both coxsackievirus and adenovirus receptor (CAR) positive and negative cancer cells. The cellular uptake result demonstrated that the relatively small size of Ad/16 kDa rPEIs (below 200 nm) was more critical to the complex's internalization than its surface charge. Cancer cell killing effect and viral production were significantly increased when oncolytic Ad (RdB/shMet, or oAd) was complexed with 16 kDa rPEI in comparison to naked oAd-, oAd/25 kDa PEI-, or oAd/32 kDa rPEI-treated cells. This increased anticancer cytotoxicity was more readily apparent in CAR-negative MCF7 cells, implying that it can be used to treat a broad range of cancer cells. Furthermore, A549 and HT1080 cancer cells treated with oAd/16 kDa rPEI had significantly decreased Met and VEGF expression compared to either naked oAd or oAd/25 kDa PEI. Overall, these results demonstrate that shMet expressing oncolytic Ad complexed with multidegradable bioreducible core-cross-linked PEI could be used as efficient and safe cancer gene therapy.
Similar articles
- Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy.
Choi JW, Kim HA, Nam K, Na Y, Yun CO, Kim S. Choi JW, et al. J Control Release. 2015 Dec 28;220(Pt B):691-703. doi: 10.1016/j.jconrel.2015.09.068. Epub 2015 Oct 3. J Control Release. 2015. PMID: 26437261 Free PMC article. - Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy.
Choi JW, Park JW, Na Y, Jung SJ, Hwang JK, Choi D, Lee KG, Yun CO. Choi JW, et al. Biomaterials. 2015 Oct;65:163-74. doi: 10.1016/j.biomaterials.2015.07.001. Epub 2015 Jul 2. Biomaterials. 2015. PMID: 26164117 - pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment and angiogenesis.
Choi JW, Jung SJ, Kasala D, Hwang JK, Hu J, Bae YH, Yun CO. Choi JW, et al. J Control Release. 2015 May 10;205:134-43. doi: 10.1016/j.jconrel.2015.01.005. Epub 2015 Jan 7. J Control Release. 2015. PMID: 25575865 Free PMC article. - Polymeric oncolytic adenovirus for cancer gene therapy.
Choi JW, Lee YS, Yun CO, Kim SW. Choi JW, et al. J Control Release. 2015 Dec 10;219:181-191. doi: 10.1016/j.jconrel.2015.10.009. Epub 2015 Oct 23. J Control Release. 2015. PMID: 26453806 Free PMC article. Review. - Recent advances in oncolytic adenovirus therapies for cancer.
Rosewell Shaw A, Suzuki M. Rosewell Shaw A, et al. Curr Opin Virol. 2016 Dec;21:9-15. doi: 10.1016/j.coviro.2016.06.009. Epub 2016 Jul 2. Curr Opin Virol. 2016. PMID: 27379906 Free PMC article. Review.
Cited by
- Progress in oncolytic viruses modified with nanomaterials for intravenous application.
Chen L, Ma Z, Xu C, Xie Y, Ouyang D, Song S, Zhao X, Liu F. Chen L, et al. Cancer Biol Med. 2023 Nov 24;20(11):830-55. doi: 10.20892/j.issn.2095-3941.2023.0275. Cancer Biol Med. 2023. PMID: 38009779 Free PMC article. Review. - Challenges and progress toward tumor-targeted therapy by systemic delivery of polymer-complexed oncolytic adenoviruses.
Thambi T, Hong J, Yoon AR, Yun CO. Thambi T, et al. Cancer Gene Ther. 2022 Oct;29(10):1321-1331. doi: 10.1038/s41417-022-00469-y. Epub 2022 Apr 20. Cancer Gene Ther. 2022. PMID: 35444290 Free PMC article. Review. - A pH- and Bioreducible Cationic Copolymer with Amino Acids and Piperazines for Adenovirus Delivery.
Thambi T, Lee J, Yoon AR, Kasala D, Yun CO. Thambi T, et al. Pharmaceutics. 2022 Mar 9;14(3):597. doi: 10.3390/pharmaceutics14030597. Pharmaceutics. 2022. PMID: 35335972 Free PMC article. - Polymeric Systems for Cancer Immunotherapy: A Review.
Le TMD, Yoon AR, Thambi T, Yun CO. Le TMD, et al. Front Immunol. 2022 Feb 22;13:826876. doi: 10.3389/fimmu.2022.826876. eCollection 2022. Front Immunol. 2022. PMID: 35273607 Free PMC article. Review. - Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements.
Jin KT, Du WL, Liu YY, Lan HR, Si JX, Mou XZ. Jin KT, et al. Cancers (Basel). 2021 Feb 3;13(4):588. doi: 10.3390/cancers13040588. Cancers (Basel). 2021. PMID: 33546172 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous