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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Chitosan Modification-Enhanced Silencing Effect of Ad5-shPDGF-D Vector in Breast Cancer Cell Line MDA-MB-231

Author(s): Ceyda Ekentok-Atıcı* and Jülide Akbuğa

Volume 20, Issue 8, 2023

Published on: 27 July, 2022

Page: [1176 - 1187] Pages: 12

DOI: 10.2174/1567201819666220429093821

Price: $65

Abstract

Background: Gene therapeutics are being developed to treat metastatic breast tumors, which are mostly resistant to conventional therapies. Targeting platelet-derived growth factor-D (PDGF-D) is a viable approach because it is known to play roles in angiogenesis and tumor growth. The success of gene therapy is largely dependent on delivery vectors, but both viral and nonviral delivery vectors have their disadvantages. Evolving hybrid vectors are being used to overcome those disadvantages.

Objectives: In this study, we aimed to prepare a recombinant adenovirus type-5 (Ad5)/chitosan hybrid vector to deliver shPDGF-D in a breast cancer cell line by the noncovalent coating of the Ad5 surface with chitosan, a natural polymer.

Methods: The Ad5/chitosan hybrid vector was prepared by the noncovalent coating of the Ad5 surface with different molecular weights (low and high) and different amounts of chitosan (12.5, 25, and 50 μg), and the effect of silencing PDGF-D was investigated in the MDA-MB-231 cell line.

Results: In vitro characterization studies showed that the noncovalent chitosan coating increased the size of the Ad5 particle and changed the surface charge from -16.53 mV to slightly neutral. In vitro cell culture studies also showed that the addition of chitosan with both low (73.61%) and high (65.86%) molecular weight increased the PDGF-D silencing efficiency of the Ad5 vector (42.44%) at 48 hours. While low-molecular-weight chitosan had faster effects, high-molecular-weight chitosan provided a more sustained effect in PDGF-D silencing.

Conclusion: The results indicate that noncovalent chitosan modification may improve the therapeutic effects of the Ad5 vector, offering the potential for further in vitro and in vivo experiments.

Keywords: Ad5, chitosan, PDGF-D, breast cancer, gene silencing, hybrid vector.

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[1]
Global Cancer Observatory. Estimated age-standardized incidence and mortality rates (World) in 2020, worldwide, females, all ages. Available from:. https://gco.iarc.fr/today/online-analysis-multi-bars?v=2020&mode=cancer&mode_population=countries&population=900&populations=900&key=asr&sex=2&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=10&group_cancer=1&include_nmsc=1&include_nmsc_other=1&type_multiple=%257B%2522inc%2522%253Atrue%252C%2522mort%2522%253Atrue%252C%2522prev%2522%253Afalse%257D&orientation=horizontal&type_sort=0&type_nb_items=%257B%2522top%2522%253Atrue%252C%2522bottom%2522%253Afalse%257D Accessed on Accessed May 12, 2021.
[2]
National Cancer Institute. Cancer stat facts: Female breast cancer. Available from: . https://seer.cancer.gov/statfacts/html/breast.html (Accessed on Mar 07, 2022).
[3]
Moo TA, Sanford R, Dang C, Morrow M. Overview of breast cancer therapy. PET Clin 2018; 13(3): 339-54.
[http://dx.doi.org/10.1016/j.cpet.2018.02.006] [PMID: 30100074]
[4]
Stoff-Khalili MA, Dall P, Curiel DT. Gene therapy for carcinoma of the breast. Cancer Gene Ther 2006; 13(7): 633-47.
[http://dx.doi.org/10.1038/sj.cgt.7700929] [PMID: 16410823]
[5]
Folkman J. Angiogenesis: An organizing principle for drug discovery? Nat Rev Drug Discov 2007; 6(4): 273-86.
[http://dx.doi.org/10.1038/nrd2115] [PMID: 17396134]
[6]
Li T, Kang G, Wang T, Huang H. Tumor angiogenesis and anti-angiogenic gene therapy for cancer. Oncol Lett 2018; 16(1): 687-702.
[http://dx.doi.org/10.3892/ol.2018.8733] [PMID: 29963134]
[7]
Sledge GW Jr. VEGF-targeting therapy for breast cancer. J Mammary Gland Biol Neoplasia 2005; 10(4): 319-23.
[http://dx.doi.org/10.1007/s10911-006-9005-5] [PMID: 16924373]
[8]
Brady N, Chuntova P, Bade LK, Schwertfeger KL. The FGF/FGFR axis as a therapeutic target in breast cancer. Expert Rev Endocrinol Metab 2013; 8(4): 391-402.
[http://dx.doi.org/10.1586/17446651.2013.811910] [PMID: 25400686]
[9]
Raica M, Cimpean AM. Platelet-Derived Growth Factor (PDGF)/PDGF receptors (PDGFR) axis as target for antitumor and antiangiogenic therapy. Pharmaceuticals (Basel) 2010; 3(3): 572-99.
[http://dx.doi.org/10.3390/ph3030572] [PMID: 27713269]
[10]
Wang Z, Kong D, Li Y, Sarkar FH. PDGF-D signaling: A novel target in cancer therapy. Curr Drug Targets 2009; 10(1): 38-41.
[http://dx.doi.org/10.2174/138945009787122914] [PMID: 19149534]
[11]
Wang Z, Ahmad A, Li Y, et al. Emerging roles of PDGF-D signaling pathway in tumor development and progression. Biochim Biophys Acta 2010; 1806(1): 122-30.
[http://dx.doi.org/10.1016/j.bbcan.2010.04.003] [PMID: 20434526]
[12]
Wu Q, Hou X, Xia J, et al. Emerging roles of PDGF-D in EMT progression during tumorigenesis. Cancer Treat Rev 2013; 39(6): 640-6.
[http://dx.doi.org/10.1016/j.ctrv.2012.11.006] [PMID: 23261166]
[13]
Li P, Zhang Z, Zhang F, Zhou H, Sun B. Effects of 3-Tetrazolyl methyl-3-Hydroxy- Oxindole Hybrid (THOH) on cell proliferation, apoptosis, and G2/M cell cycle arrest occurs by targeting Platelet-Derived Growth Factor D (PDGF-D) and the MEK/ERK signaling pathway in human lung cell lines SK-LU-1, A549, and A-427. Med Sci Monit 2018; 24: 4547-54.
[http://dx.doi.org/10.12659/MSM.909125] [PMID: 29961751]
[14]
Zhao L, Zhang C, Liao G, Long J. RNAi-mediated inhibition of PDGF-D leads to decreased cell growth, invasion and angiogenesis in the SGC-7901 gastric cancer xenograft model. Cancer Biol Ther 2010; 9(1): 42-8.
[http://dx.doi.org/10.4161/cbt.9.1.10282] [PMID: 20087065]
[15]
Han Y, Guo XH, Zheng QF, Zhu YL, Fan YY, Zhang XY. Down-regulation of platelet-derived growth factor-D expression blockades NF-κB pathway to inhibit cell proliferation and invasion as well as induce apoptosis in esophageal squamous cell carcinoma. Mol Biol Rep 2013; 40(3): 2473-83.
[http://dx.doi.org/10.1007/s11033-012-2328-y] [PMID: 23187740]
[16]
Akbuga J, Ozbas-Turan S, Kabasakal L, Salva E, Ozkan N. PDGF-D inhibition by using chitosan:siRNA complexes in breast cancer model of rat. Mol Ther 2015; 23: S236.
[http://dx.doi.org/10.1016/S1525-0016(16)34203-4]
[17]
Ekentok C, Özbaş ST, Akbuğa J. In vitro gene silencing effect of chitosan/shRNA PDGF-D nanoparticles in breast cancer. Marmara Pharm J 2017; 21(4): 793-803.
[http://dx.doi.org/10.12991/mpj.2017.21]
[18]
Lambeth LS, Smith CA. Short hairpin RNA-mediated gene silencing. Methods Mol Biol 2013; 942: 205-32.
[http://dx.doi.org/10.1007/978-1-62703-119-6_12] [PMID: 23027054]
[19]
Huang PI, Lo WL, Cherng JY, Chien Y, Chiou GY, Chiou SH. Non-viral delivery of RNA interference targeting cancer cells in cancer gene therapy. Curr Gene Ther 2012; 12(4): 275-84.
[http://dx.doi.org/10.2174/156652312802083576] [PMID: 22856602]
[20]
Merten O, Gaillet B. Viral vectors for gene therapy and gene modification approaches. Biochem Eng J 2016; 108: 98-115.
[http://dx.doi.org/10.1016/j.bej.2015.09.005]
[21]
Volpers C, Kochanek S. Adenoviral vectors for gene transfer and therapy. J Gene Med 2004; 6(S1) (Suppl. 1): S164-71.
[http://dx.doi.org/10.1002/jgm.496] [PMID: 14978759]
[22]
Kasala D, Choi JW, Kim SW, Yun CO. Utilizing adenovirus vectors for gene delivery in cancer. Expert Opin Drug Deliv 2014; 11(3): 379-92.
[http://dx.doi.org/10.1517/17425247.2014.874414] [PMID: 24392755]
[23]
Jang JH, Schaffer DV, Shea LD. Engineering biomaterial systems to enhance viral vector gene delivery. Mol Ther 2011; 19(8): 1407-15.
[http://dx.doi.org/10.1038/mt.2011.111] [PMID: 21629221]
[24]
Sun Y, Lv X, Ding P, et al. Exploring the functions of polymers in adenovirus-mediated gene delivery: Evading immune response and redirecting tropism. Acta Biomater 2019; 97: 93-104.
[http://dx.doi.org/10.1016/j.actbio.2019.06.059] [PMID: 31386928]
[25]
Saranya N, Moorthi A, Saravanan S, Devi MP, Selvamurugan N. Chitosan and its derivatives for gene delivery. Int J Biol Macromol 2011; 48(2): 234-8.
[http://dx.doi.org/10.1016/j.ijbiomac.2010.11.013] [PMID: 21134396]
[26]
Borchard G. Chitosans for gene delivery. Adv Drug Deliv Rev 2001; 52(2): 145-50.
[http://dx.doi.org/10.1016/S0169-409X(01)00198-3] [PMID: 11718938]
[27]
Kawamata Y, Nagayama Y, Nakao K, et al. Receptor-independent augmentation of adenovirus-mediated gene transfer with chitosan in vitro. Biomaterials 2002; 23(23): 4573-9.
[http://dx.doi.org/10.1016/S0142-9612(02)00203-X] [PMID: 12322978]
[28]
Zhong H, Lei X, Qin L, Wang J, Hung T. Augmentation of adenovirus 5 vector-mediated gene transduction under physiological pH conditions by a chitosan/NaHCO3 solution. Gene Ther 2011; 18(3): 232-9.
[http://dx.doi.org/10.1038/gt.2010.129] [PMID: 20882055]
[29]
Wang IJ, Jhuang MC, Chen YH, Yeh LK, Liu CY, Young TH. Chitosan modification of adenovirus to modify transfection efficiency in bovine corneal epithelial cells. PLoS One 2010; 5(8): e12085.
[http://dx.doi.org/10.1371/journal.pone.0012085] [PMID: 20711466]
[30]
Muzzarelli RA. Colorimetric determination of chitosan. Anal Biochem 1998; 260(2): 255-7.
[http://dx.doi.org/10.1006/abio.1998.2705] [PMID: 9657888]
[31]
Grünwald GK, Vetter A, Klutz K, et al. Systemic image-guided liver cancer radiovirotherapy using dendrimer-coated adenovirus encoding the sodium iodide symporter as theranostic gene. J Nucl Med 2013; 54(8): 1450-7.
[http://dx.doi.org/10.2967/jnumed.112.115493] [PMID: 23843567]
[32]
Huang M, Li G, Pan T, et al. A novel multi-target RNAi adenovirus inhibits hepatoma cell proliferation, migration, and induction of angiogenesis. Oncotarget 2016; 7(36): 57705-13.
[http://dx.doi.org/10.18632/oncotarget.9531] [PMID: 27221035]
[33]
Yoo JY, Kim JH, Kwon YG, et al. VEGF-specific short hairpin RNA-expressing oncolytic adenovirus elicits potent inhibition of angiogenesis and tumor growth. Mol Ther 2007; 15(2): 295-302.
[http://dx.doi.org/10.1038/sj.mt.6300023] [PMID: 17235307]
[34]
Song B, Liu X, Wang Q, et al. Adenovirus-mediated shRNA interference against HSV-1 replication in vitro. J Neurovirol 2016; 22(6): 799-807.
[http://dx.doi.org/10.1007/s13365-016-0453-4] [PMID: 27566181]
[35]
Wang W, Li W, Ma N, Steinhoff G. Non-viral gene delivery methods. Curr Pharm Biotechnol 2013; 14(1): 46-60.
[http://dx.doi.org/10.2174/1389201011314010008] [PMID: 23437936]
[36]
Huang M, Fong CW, Khor E, Lim LY. Transfection efficiency of chitosan vectors: Effect of polymer molecular weight and degree of deacetylation. J Control Release 2005; 106(3): 391-406.
[http://dx.doi.org/10.1016/j.jconrel.2005.05.004] [PMID: 15967533]
[37]
Lu J, Hu Z, Yang M, et al. Downregulation of PDGF-D inhibits proliferation and invasion in breast cancer MDA-MB-231 cells. Clin Breast Cancer 2022; 22(2): e173-83.
[http://dx.doi.org/10.1016/j.clbc.2021.06.002] [PMID: 34272173]

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