Nanolipoparticles-mediated MDR1 siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR1 expression in xenograft model of human breast cancer | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 11، دوره 18، شماره 4، تیر 2015، صفحه 385-392 اصل مقاله (1.76 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2015.4288 | ||
| نویسندگان | ||
| Mahnaz Nourbakhsh1، 2، 3؛ Mahmoud Reza Jaafari2، 3؛ Hermann Lage4؛ Khalil Abnous5؛ Fatemeh mosaffa3؛ Ali Badiee2؛ Javad Behravan* 1، 6 | ||
| 1Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 2Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 3Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 4Charite´ Campus Mitte, Institute of Pathology, Charite´platz 1, D-10117 Berlin, Germany | ||
| 5Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 6Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. | ||
| چکیده | ||
| Objective(s): P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. We investigated a special class of PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), for siRNA-mediated P-gp downregulation. Materials and Methods: NLPs were prepared based on low detergent dialysis method. After characterization, we evaluated the effect of NLPs on siRNA delivery, and P-gp downregulation compared to oligofectamineTM (OFA) in vitro and in vivo. Results: Our results showed a significant decrease in P-gp expression and subsequent enhancement of chemosensitivity to doxorubicin in vitro. Although the effectiveness of NLPs for in vitro siRNA delivery compared to OFA was limited, the results of in vivo studies showed noticeable effectiveness of NLPs for systemic siRNA delivery. siRNA delivery using NLPs could downregulate MDR1 in tumor cells more than 80%, while OFA had a reverse effect on MDR1 expression in vivo. Conclusion: The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy. | ||
| کلیدواژهها | ||
| Breast Cancer؛ Gene Therapy؛ Liposome؛ Multidrug resistance؛ siRNA delivery؛ Tumor targeting | ||
| مراجع | ||
|
1. Mechetner E, Kyshtoobayeva A, Zonis S, Kim H, Stroup R, Garcia R, et al. Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res 1998; 4:389-398.
2. Taheri M, Mahjoubi F, Omranipour R. Effect of MDR1 polymorphism on multidrug resistance expression in breast cancer patients. Genet Mol Res 2010; 9:34-40.
3. Liscovitch M, Lavie Y. Cancer multidrug resistance: a review of recent drug discovery research. IDrugs 2002; 5:349-355.
4. Abbasi M, Lavasanifar A, Uludaˇ H. Recent attempts at RNAi‐mediated P‐glycoprotein downregulation for reversal of multidrug resistance in cancer. Med Res Rev 2013; 33:33-53.
5. Gao Y, Liu XL, Li XR. Research progress on siRNA delivery with nonviral carriers. Int J Nanomed 2011; 6:1017-1025.
6. Huang L, Liu Y. In vivo delivery of RNAi with lipid-based nanoparticles. Annu Rev Biomed Eng 2011; 13:507-530.
7. Li W, Szoka FC, Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm Res 2007; 24:438-449.
8. Li W, Huang Z, MacKay JA, Grube S, Szoka FC, Jr. Low-pH-sensitive poly(ethylene glycol) (PEG)-stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery. J Gene Med 2005; 7:67-79.
9. Rastgoo M, Hosseinzadeh H, Alavizadeh H, Abbasi A, Ayati Z, Jaafari MR. Antitumor activity of PEGylated nanoliposomes containing crocin in mice bearing C26 colon carcinoma. Planta Med 2013; 79:447-451.
10. Nourbakhsh M, Behravan J, Lage H, Abnous K, Mosaffa F, Badiee A, et al. Nanolipoparticles-mediated MDR1 siRNA delivery: preparation, characterization and cellular uptake. Nanomed J 2015;2:39-45.
11. Stierle V, Laigle A, Jolles B. The reduction of P-glycoprotein expression by small interfering RNAs is improved in exponentially growing cells. Oligonucleotides 2004; 14:191-198.
12. Mosaffa F, Lage H, Afshari JT, Behravan J. Interleukin-1 beta and tumor necrosis factor-alpha increase ABCG2 expression in MCF-7 breast carcinoma cell line and its mitoxantrone-resistant derivative, MCF-7/MX. Inflamm Res 2009; 58:669-676.
13. Kanzaki A, Takebayashi Y, Ren XQ, Miyashita H, Mori S, Akiyama S, et al. Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743. Mol Cancer Ther 2002; 1:1327-1334.
14. Kalalinia F, Elahian F, Hassani M, Kasaeeian J, Behravan J. Phorbol ester TPA modulates chemoresistance in the drug sensitive breast cancer cell line MCF-7 by Inducing expression of drug efflux transporter ABCG2. Asian Pac J Cancer Prev 2012; 13:2979-2984.
15. Stege A, Kruhn A, Lage H. Overcoming multidrug resistance by RNA interference. Methods Mol Biol 2010; 596:447-465.
16. Ebrahimnejad P, Dinarvand R, Sajadi A, Jaafari MR, Nomani AR, Azizi E, et al. Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines. Nanomed Nanotechnol Biol Med 2010; 6:478-485.
17. Hoogenhout J, Kazem I, Jerusalem CR, Bakkeren JA, de Jong J, Kal HB, et al. Growth pattern of tumor xenografts in Wistar rats after treatment with cyclophosphamide, total lymphoid irradiation and/or cyclosporin A. Int J Radiat Oncol Biol Phys 1983; 9:871-879.
18. Fingert HJ, Chen Z, Mizrahi N, Gajewski WH, Bamberg MP, Kradin RL. Rapid growth of human cancer cells in a mouse model with fibrin clot subrenal capsule assay. Cancer Res 1987; 47:3824-3829.
19. Jalali SA, Sankian M, Tavakkol-Afshari J, Jaafari MR. Induction of tumor-specific immunity by multi-epitope rat HER2/neu-derived peptides encapsulated in LPD Nanoparticles. Nanomed Nanotechnol Biol Med 2012; 8:692-701.
20. Foldvari M, Jaafari MR, Radhi J, Segal D. Efficacy of the antiadhesin octyl O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl)-(1-4)-2-O-propyl-beta-D-ga lactopy-ranoside (Fimbrigal-P) in a rat oral candidiasis model. Antimicrob Agents Chemother 2005; 49:2887-2894.
21. Muller C, Laurent G, Ling V. P-glycoprotein stability is affected by serum deprivation and high cell density in multidrug-resistant cells. J Cell Physiol 1995; 163:538-544.
22. Persengiev SP, Zhu X, Green MR. Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 2004; 10:12-18.
23. Wheeler JJ, Palmer L, Ossanlou M, MacLachlan I, Graham RW, Zhang YP, et al. Stabilized plasmid-lipid particles: construction and characterization. Gene Ther 1999; 6:271-281.
24. Fenske DB, MacLachlan I, Cullis PR. Stabilized plasmid-lipid particles: a systemic gene therapy vector. Methods Enzymol 2002; 346:36-71.
25. Harvie P, Wong FM, Bally MB. Use of poly(ethylene glycol)-lipid conjugates to regulate the surface attributes and transfection activity of lipid-DNA particles. J Pharm Sci 2000; 89:652-663.
26. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 2005; 11:263-270.
27. Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J Mol Biol 2005; 348:1079-1090.
28. Kang Y, Perry RR. Effect of α-interferon on p-glycoprotein expression and function and on verapamil modulation of doxorubicin resistance. Cancer Res 1994; 54:2952-2958.
29. Akhtar S, Benter I. Toxicogenomics of non-viral drug delivery systems for RNAi: Potential impact on siRNA-mediated gene silencing activity and specificity. Adv Drug Deliv Rev 2007; 59:164-182.
30. Jiang J, Yang SJ, Wang JC, Yang LJ, Xu ZZ, Yang T, et al. Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin. Eur J Pharm Biopharm 2010; 76:170-178.
31. Patil YB, Swaminathan SK, Sadhukha T, Ma L, Panyam J. The use of nanoparticle-mediated targeted gene silencing and drug delivery to overcome tumor drug resistance. Biomaterials 2010; 31:358-365.
32. Wu SY, Singhania A, Burgess M, Putral LN, Kirkpatrick C, Davies NM, et al. Systemic delivery of E6/7 siRNA using novel lipidic particles and its application with cisplatin in cervical cancer mouse models. Gene Ther 2011; 18:14-22.
33. Zimmermann TS, Lee AC, Akinc A, Bramlage B, Bumcrot D, Fedoruk MN, et al. RNAi-mediated gene silencing in non-human primates. Nature 2006; 441:111-114.
34. Wu SY, Putral LN, Liang M, Chang HI, Davies NM, McMillan NA. Development of a novel method for formulating stable siRNA-loaded lipid particles for in vivo use. Pharm Res 2009; 26:512-522. | ||
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