Targeted Drug Delivery and Vaccinology Approaches Using Virus-like Particles for Cancer

Abstract

Nanotechnology has the potential to make significant alterations in the treatment of diseases such as cancer through targeted drug delivery nanoparticles. Virus-like particles (VLPs) are composed of the capsid proteins that do not carry the viral genome and are also noninfectious. VLPs are self-assembling competent protein structures with identical or highly related structures to their corresponding native viruses. VLPs that have precise 3D nanostructures exhibit a notable diversity in shapes and structures. They can be produced in large quantities through biological amplification and growth. External protein inserts can be displayed through genetic methods or chemical modifications. Functionalized VLPs when used as delivery systems have the ability to target with specificity and can attract macrophages for the destruction of cancer cells. The capability to target tumors for the delivery of therapeutic agents is an important goal of the design approaches of VLPs. Against the current problems in cancer therapies, delivery systems using VLPs are an arising and promising field with the potential to exhibit solutions. Cancer therapies require specific targeting of the diagnostic element or the drug to tumor cells without binding to or affecting healthy cells and tissues. Specialization of the VLPs provides an opportunity for using them as site-specific drug delivery systems in cancer therapy while reducing the systemic toxicity and the overall damage to healthy cells. With fewer side effects, immunotherapy is also a promising alternative for cancer treatment by primarily activating the host’s immune system. Cancer vaccines are aimed at inducing an immune response in the host, thereby generating a defensive mechanism against tumor cells. VLPs can be used as a vaccine without the requirement of any adjuvant due to their naturally optimized particle size and their repetitive structural order. Therefore, the aim of this review is to provide basic information about VLPs and describe previous research on VLPs used as drug and vaccine delivery systems and their applications in different types of cancer.

Keywords

• nanocarriers,virus-like particles,drug delivery,cancer vaccine,cancer therapy

References

1. Abbing A, Blaschke UK, Grein S, Kretschmar M, Stark CM, Thies MJ, Walter J, Weigand M, Woith DC, Hess J et al. (2004) Efficient intracellular delivery of a protein and a low molecular weight substance via recombinant polyo mavirus-like particles, J. Biol. Chem., 279:27410-27421.
2. Aljabali AA, Shukla S, Lomonossoff GP, Steinmetz NF, Evans DJ (2013) CPMV-DOX delivers, Mol. Pharm., 10:3-10.
3. Alpar HO, Özsoy Y, Cevher E (2014) Nanotaşıyıcıların Aşı Uygulamasında Kullanılması. In: Zırh-Gürsoy A (ed.) Nanofarmasötikler ve Uygulamaları, Kontrollü Salım Sistemler Derneği, İstanbul, pp.277-286.
4. Ashley CE, Carnes EC, Phillips GK, Durfee PN, Buley MD, Lino CA, Padilla DP, Phillips B, Carter MB, Willman CL et al. (2011) Cell-specific delivery of diverse cargos by bacteriophage MS2 virus-like particles, ACS Nano, 5:5729-5745.
5. Blokhina EA, Kupriyanov VV, Ravin NV, Skryabin KG (2013) The Method of Noncovalent in vitro Binding of Target Proteins to Virus-Like Nanoparticles Formed by Core Antigen of Hepatitis B Virus, Dokl. Akad. Nauk., 448: 719–721.
6. Choi KM, Kim K, Kwon IC, Kim IS, Ahn HJ (2013) Systemic delivery of siRNA by chimeric capsid protein: tumor targeting and RNAi activity in vivo, Mol. Pharm., 10:18-25.
7. Chou MI, Hsieh YF, Wang M, Chang JT, Chang D, Zouali M, Tsay GJ (2010) In vitro and in vivo targeted delivery of IL-10 interfering RNA by JC virus-like particles, J. Biomed. Sci., 17:51.
8. Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, García P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Joura EA, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan JT, Maansson R, Lu S, Vuocolo S, Hesley TM, Barr E, Haupt R. (2010) Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ., 341:c3493.

9. Deo VK, Kato T, Park EY (2015) Chimeric Virus-Like Particles Made Using GAG and M1 Capsid Proteins Providing Dual Drug Delivery and Vaccination Platform, Mol. Pharm., 12:839−845.
10. Fua Y, Li J (2016) A novel delivery platform based on Bacteriophage MS2 virus-like particles, Virus Res., 211:9–16. Galaway FA, Stockley PG (2013) MS2 viruslike particles: a robust, semisynthetic targeted drug delivery platform, Mol. Pharm., 10:59-68.
11. Glaxosmithkline Vaccine HPVSG, Romanowski B, De Borba PC, Naud PS, Roteli-Martins CM, De Carvalho NS, Teixeira JC, Aoki F, Ramjattan B, Shier RM, Somani R, Barbier S, Blatter MM, Chambers C, Ferris D, Gall SA, Guerra FA, Harper DM, Hedrick JA, Henry DC, Korn AP, Kroll R,Moscicki AB, Rosenfeld WD, Sullivan BJ, Thoming CS, Tyring SK, Wheeler CM, Dubin G, Schuind A, Zahaf T, Greenacre M, Sgriobhadair A (2009) Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet., 374(9706):1975–1985.
12. Ghasparian A, Riedel T, Koomullil J, Moehle K, Gorba C, Svergun DI, Perriman AW, Mann S, Tamborrini M, Pluschke G, Robinson JA (2011) Engineered Synthetic Virus-Like Particles and Their Use in Vaccine Delivery, ChemBioChem, 12:100 – 109.
13. Goldinger SM, Imhof L, Willers J, French LE, Dummer R, (2010) Phase II clinical trial using Virus-Like Particle (VLP) vaccine including a melan-A analogon and imiquimod”, Melanoma Res., 20:e56.
14. Grgacic EV, Anderson DA (2006) Virus-like particles: Passport to immune recognition, Methods, 40:60– 65.
15. Hauser P, Voet P, Simoen E (1987) Immunological properties of recombinant HbsAg produced in yeast. Postgrad Med J., 63:83–91.
16. Hourvitz A1, Mosseri R, Solomon A, Yehezkelli Y, Atsmon J, Danon YL, Koren R, Shouval D (1996) Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine containing Pre S antigens: a preliminary report. J Viral Hepat.,3(1):37-42.
17. Huang X, Wang X, Jun Zhang J, Xia N, Zhao Q (2017) Escherichia coli-derived virus-like particles in vaccine development. Vaccines, doi:10.1038/s41541-017-0006-8.
18. Kaczmarczyk SJ, Sitaraman K, Young HA, Hughes SH, Chatterjee DK (2011) Protein delivery using engineered virus-like particles, Proc. Natl. Acad. Sci., 108:16998-17003.
19. Kapusta J, Modelska A, Figlerowicz M, Pniewski T, Letellier M, Lisowa O, Yusibov V, Koprowski H, Plucienniczak A, Legocki AB. (1999)A plant-derived edible vaccine against hepatitis B virus. FASEB J., 13(13):1796-9.
20. Kaufmann AM, Nitschmann S (2010) Vaccine against human papillomavirus: PATRICIA Study (PApilloma TRIal against Cancer In young Adults). Der Internist., 51(3):412–413.
21. Kreimer AR, Gonzalez P, Katki HA, Porras C, Schiffman M, Rodriguez AC, Solomon D, Jiménez S, Schiller JT, Lowy DR, van Doorn LJ, Struijk L, Quint W, Chen S, Wacholder S, Hildesheim A, Herrero R; CVT Vaccine Group. (2011) Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial. The lancet oncology., 12(9):862–870.
22. Kyriakopoulos S, Kontoravdi C (2013) Analysis of the landscape of biologicallyderived pharmaceuticals in Europe: dominant production systems, molecule types on the rise and approval trends. Eur. J. Pharm. Sci., 48: 428–441.
23. Kushnir N, Streatfield SJ, Yusibov V (2012) Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development. Vaccine., 31(1):58-83.
24. Lacson E, Teng M, Ong J, Vienneau L, Ofsthun N, Lazarus JM (2005) Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end-stage renal disease. Hemodial Int., 9(4):367-75.
25. Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsagué X, Skinner SR, Apter D, Naud P, Salmerón J, Chow SN, Kitchener H, Teixeira JC, Hedrick J, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, De Carvalho NS, Germar MJ, Peters K, Mindel A, De Sutter P, Bosch FX, David MP, Descamps D, Struyf F, Dubin G; HPV PATRICIA Study Group. (2012) Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. The lancet oncology., 13(1):89–99.
26. Li SW, Zhao Q, Wu T, Chen S, Zhang J, Xia NS. (2015) The development of a recombinant hepatitis E vaccine HEV 239. Hum. vaccin immunother., 11: 908–914.
27. Lobaina Y, Aguiar J, Pentón E , Aguilar JC (2015) Demonstration of safety, immunogenicity and evidences of efficacy of the therapeutic vaccine candidate HeberNasvac and characterization of chronic hepatitis B patient populations. Biotecnología Aplicada., 32: 3511–3513.
28. Lockney DM, Guenther RN, Loo L, Overton W, Antonelli R, Clark J, Hu M, Luft C, Lommel SA, Franzen S (2011) The Red clover necrotic mosaic virus capsid as a multifunctional cell targeting plant viral nanoparticle, Bioconjug. Chem., 22:67-73. Lua LH, Connors NK, Sainsbury F, Chuan YP, Wibowo N, Middelberg AP (2014) Bioengineering virus-like particles as vaccines. Biotechnol. Bioeng., 111: 425–440.
29. Ma Y et al. (2012) Virus-based nanocarriers for drug delivery, Adv. Drug Deliv. Rev., 64:811–825.
30. Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley DJ, Alvarez FB, Bautista OM, Jansen KU, Barr E. (2006) Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstetrics and gynecology., 107(1):18–27. Manzenrieder F, Luxenhofer R, Retzlaff M, Jordan R, Finn MG, (2011) Stabilization of Virus-like Particles with Poly(2-oxazoline)s, Angew. Chem. Int. Ed., 50:2601 –2605.
31. Matassov D, Cupo A, Galarza JM, (2007) A Novel Intranasal Virus-Like Particle (VLP) Vaccine Designed to Protect against the Pandemic 1918 Influenza A Virus (H1N1), Viral Immunol., 20(3):441-52.
32. Molino NM, Wang S (2014) Caged protein nanoparticles for drug delivery, Curr. Opi. Biotechnol., 28:75–82.
33. Niikura K, Sugimura N, Musashi Y, Mikuni S, Matsuo Y, Kobayashi S, Nagakawa K, Takahara S, Takeuchi C, Sawa H et al. (2013) Virus-like particles with removable cyclodextrins enable glutathionetriggered drug release in cells, Mol. Biosyst., 9:501-507.
34. Parkin, DM, (2006) The global health burden of infection-associated cancers in the year 2002, Int. J. Cancer, 118: 3030–3044.
35. Proffitt A (2012) First HEV vaccine approved. Nature Biotechnology, doi:10.1038/nbt0412-300a.
36. Ren Y, Wong SM, Lim LY (2007) Folic acid-conjugated protein cages of a plant virus: a novel delivery platform for doxorubicin, Bioconjug. Chem., 18:836-843.
37. Rosenthal et al. (2014) Pathogen-like particle vaccines: biomimetic vaccine carriers engineered at the nanoscale, Curr. Opi. Biotechnol., 28:51–58.
38. Schiller JT, Castellsague X, Garland SM (2012) A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine, 30: F123–F138.
39. Shan L, Cui S, Du C, Wan S, Qian Z, Achilefu S, Gu Y (2012) A paclitaxel- conjugated adenovirus vector for targeted drug delivery for tumor therapy, Biomater., 33:146-162.
40. Shen L, Zhou J, Wang Y, Kang N, Ke X, Bi S, Ren L (2015) Efficient Encapsulation of Fe3O4 Nanoparticles into Genetically Engineered Hepatitis B Core Virus-Like Particles Through a Specific Interaction for Potential Bioapplications, Small Journal, Wiley-VCH GmbH & Co.
41. Shirbaghaee Z, Bolhassani A, (2016) Different Applications of Virus-Like Particles in Biology and Medicine: Vaccination and Delivery Systems, Biopolym., 105:113-132.
42. Smith JD, Morton LD, Ulery BD (2015) Nanoparticles as synthetic vaccines, Curr. Opin. Biotechnol., 34:217–224.
43. Teunissen EA, Raad M, Mastrobattista E (2013) Production and biomedical applications of virus-like particles derived from polyomaviruses, J. Control. Release, 172: 305–321.
44. Venters C, Graham W, Cassidy W (2004) Recombivax-HB: perspectives past, present and future. Expert Rev. Vaccines., 3, 119–129.
45. Wei M, Zhang X, Yu H, Tang ZM, Wang K, Li Z, Zheng Z, Li S, Zhang J, Xia N, Zhao Q (2014) Bacteria expressed hepatitis E virus capsid proteins maintain virionlike epitopes. Vaccine, 32: 2859–2865.
46. West DJ, Calandra GB (1996) Vaccine induced immunologic memory for hepatitis B surface antigen: Implications for policy on booster vaccination. Vaccine., 14:1019– 1027.
47. Yildiz I, Shukla S, Steinmetz NF, (2011) Applications of viral nanoparticles in medicine, Curr. Opi. Biotechnol., 22:901–908.
48. Zeng Q, Wen H, Wen Q, Chen X, Wang Y, Xuan W, Liang J, Wan S (2013) Cucumber mosaic virus as drug delivery vehicle for doxorubicin, Biomater., 34:4632-4642.
49. Zhao Q, Li S, Yu H, Xia N, Modis Y (2013) Virus-like particle-based human vaccines: quality assessment based on structural and functional properties, Trends Biotechnol., 31(11):654-63.
50. Zhao L, Setha A, Wibowo N, Zhao CX, Mitter N, Yu C, Middelberg A (2014) Nanoparticle vaccines, Vaccine, 32:327– 337.
51. Zhao Q, Potter CS, Carragher B, Lander G, Sworen J, Towne V, Abraham D, Duncan P, Washabaugh MW, Sitrin RD (2014) Characterization of virus-like particles in GARDASIL® by cryo transmission electron microscopy, Hum. Vaccines & Immunother., 10:3, 734–739.
52. Zhou Z, Bedwell GJ, Li R, Prevelige PE, Gupta JA (2014) Formation mechanism of chalcogenide nanocrystals confined inside genetically engineered virus-like particles, Sci. Rep., 4:3832.
53. Zochowska M, Paca A, Schoehn G, Andrieu JP, Chroboczek J, Dublet B, Szolajska E (2009) Adenovirus dodecahedron, as a drug delivery vector, PLoS One, 4:e5569.
54. zur Hausen, H, (2001) Viruses in human cancers, Curr. Sci., 81:523–527.
55. (2015) ABX203 (HeberNasvac) granted cuban marketing authorization to treat chronic Hepatitis B. Available at: http://www.abivax.com/images/pdf/ 151208_ABX203_Cuban_Authorization.pdf Accessed 29.03.2017.