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Demirci H, Wang Y, Li Q, Lin C- mao, Kotov NA, Diniz Grisolia AB, Guo JL. Penetration of Carbon Nanotubes into the Retinoblastoma Tumor after Intravitreal Injection in LHBETATAG Transgenic Mice Reti-noblastoma Model. JOVR [Internet]. 2020Oct.25 [cited 2024Jul.17];15(4):446–452. Available from: https://knepublishing.com/index.php/JOVR/article/view/7778

https://doi.org/10.18502/jovr.v15i4.7778

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authors

  • Hakan Demirci

    Hakan Demirci

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan
    https://orcid.org/0000-0003-1593-1476
  • Yichun Wang

    Yichun Wang

    Biointerfaces Institute, University of Michigan; Department of Chemical Engineering
  • Qiaochu Li

    Qiaochu Li

    Electrical Engineering and Computer Science, University of Michigan
  • Cheng-mao Lin

    Cheng-mao Lin

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan
  • Nicholas A Kotov

    Nicholas A Kotov

    Biointerfaces Institute, University of Michigan
  • Anna Beatriz Diniz Grisolia

    Anna Beatriz Diniz Grisolia

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan
  • Jay L Guo

    Jay L Guo

    Electrical Engineering and Computer Science, University of Michigan

Published Date

  • Oct 25, 2020
This journal is publishing all the articles under Creative Commons Attribution License CC BY 4.0.

Penetration of Carbon Nanotubes into the Retinoblastoma Tumor after Intravitreal Injection in LHBETATAG Transgenic Mice Reti-noblastoma Model

Journal of Ophthalmic and Vision Research (JOVR) / October–December 2020, Volume 15, Issue 4 / Pages 446–452

Abstract

Purpose: To evaluate the penetration of carbon nanotubes (CNTs) throughout retinoblastoma in a transgenic mice model.


Methods: CNTs functionalized with fluorescein isothiocyanate and targeting ligands biotin (CTN-FITC-Bio, 0.5mg/ml), or folic acid (CNT-FITC-FA, 0.5mg/ml) were injected into the vitreous of one eye of LHBETATAG transgenic mice. Other eye did not receive any injection and was used as control. Three mice were sacrificed at days 1, 2, and 3. Eyes were enucleated and stained with 4,6-diamidino-2-phenylindole. The sections were imaged by fluorescent microscope. The images were transformed into grey-scale in MATLAB for intensity analysis. Background intensity was normalized by marking squares outside the eyeball and using the mean intensity of these squares. Fluorescent intensity (FI) for each image was measured by calculating the intensity of a same-sized square within retinoblastoma.


Results: Nine eyes of nine mice were included in each CNT-FITC-Bio and CNT-FITC-FA groups. The mean FI in CNT-FITC-Bio was 52.08 ± 6.33, 53.62 ± 9.00, and 65.54 ± 5.14 in days 1, 2, and 3, respectively. The mean FI in CNT-FITC-FA was 50.28 ± 7.37, 59.21 ± 6.43, and 58.38 ± 2.32 on days 1, 2, and 3, respectively. FI was significantly higher in eyes injected with CNT-FITC-Bio and CNT-FITC-FA compared to the control eyes (P = 0.02). There was no difference in FI between eyes with CNT-FITC-Bio and CNT-FITC-FA, and FI remained stable on days 1–3 in CNT-FITC-Bio, CNT-FITC-FA, and control eyes (P > 0.05).


Conclusion: We observed higher FI in eyes with CNT-FITC-Bio and CNT-FITC-FA compared to control eyes, showing penetration of CNTs throughout retinoblastoma. CNTs can be a carrier candidate for imaging or therapeutic purposes in retinoblastoma.

Keywords:

NA

References
1. Young JL, Smith MA, Roffers SD, Liff JM, Bunin GR. Retinoblastoma. In: Ries LA, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, et al., editors. Cancer incidence and survival among children and adolescents: United States SEER program 1975–1995. Maryland: National Cancer 4 Institute, SEER Program; 2012 .

2. Shields CL, DePotter P, Himelstein BP, Shields JA, Meadows AT, Maris JM. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol 1996;114:1330–1338.

3. Murphree AL, Villablanca JG, Deegan WF, Sato JK, Malogolowkin M, Fisher A, et al. Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Arch Opthalmol 1996;114:1348–1356.

4. Gallie BL, Budning A, DeBoer GKoren G, Verje, Thiessen JJ, e Z, et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophthalmol 1996;114:1321–1328.

5. Shields CL, Jorge R, Say EA, Magrath G, Alset A, Caywood E, et al. Unilateral retinoblastoma managed with intravenous chemotherapy versus intra-arterial chemotherapy. Outcomes based on the international classification of retinoblastoma. Asia Pac J Ophthalmol 2016;5:97–103.

6. Manjandavida FP, Stathopoulos C, Zhang J, Honavar SG, Shields CL. Intra-arterial chemotherapy in retinoblastoma - a paradigm change. Indian J Ophthalmol 2019;67:740– 754.

7. Munier FL, Mosimann P, Puccinelli F, Gaillard MC, Stathopoulos C, Houghton S, et al. First-line intraarterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment. Br J Ophthalmol 2017;101:1086–1093.

8. Abramson DH, Marr BP, Dunkel IJ, Brodie S, Zabor EC, Driscoll SJ, et al. Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results. Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year result. Br J Ophthalmol 2012;96:499–502.

9. Shields CL, Alset AE, Say EA, Caywood E, Jabbour P, Shields JA. Retinoblastoma control with primary intraarterial chemotherapy: outcomes before and during the intravitreal chemotherapy era. J Pediatr Ophthalmol Strabismus 2016;53:275–284.

10. Ghassemi F, Amoli FA. Pathological findings in enucleated eyes after intravitreal melphalan injection. Int Ophthalmol 2014;34:533–540.

11. REF Tang Z, Wang Y, Podsiadlo P, Kotov NA. Biomedical applications of layer-by-layer assembly: from biomimetics to tissue engineering. Adv Mater 2006;18:3203–3224.

12. Gheith MK, Pappas TC, Liopo AV, Sinani V, Shim BS, Motamedi M, et al. Stimulation of neural cells by lateral currents in conductive LBL films of single-walled carbon nanotubes. Adv Mater 2006;18:2975–2979.

13. Mohajeri M, Behnam B, Sahebkar A. Biomedical applications of carbon nanomaterials: drug and gene delivery potentials. J Cell Physiol 2018;234:298–319.

14. Yang K, Liu Z. In vivo biodistribution, pharmacokinetics, and toxicology of carbon nanotubes. Curr Drug Metabol 2012;13:1057–1067.

15. Singh R, Pantarotto D, Lacerda L, Patorin G, Klumpp C, Prato M, et al. Tissue Biodistribution and Blood Clearance Rates of Intravenously Administered Carbon Nanotube Radiotracers. Proc Natl Acad Sci USA 2006;103:3357– 3362.

16. Sager TM, Wolfarth MW, Andrew M, Hubbs A, Friend S, Chen TH, et al. Effect of Multi-Walled Carbon Nanotube Surface Modification on Bioactivity in the C57bl/6 Mouse Model. Nanotoxicology 2014;8:317–327.

17. Wang Y, Bahng JH, Che Q, Han J, Kotov NA. Anomalously fast diffusion of targeted carbon nanotubes in cellular spheroids. ACS Nano 2015;9:8231–8238.

18. Kansara V, Paturi D, Luo S, Gaudana R, Mitra AK. Folic acid transport via high affinity carrier-mediated system in human retinoblastoma cells. Int J Pharm 2008;355:210– 219.

19. Kansara V, Luo S, Balasubrahmanyam B, Pal D, Mitra AK. Biotin uptake and cellular translocation in human derived retinoblastoma cell line (Y-79): a role of hSMVT system. Int J Pharm 2006;312:43–52.

20. Albert DM, Griep AE, Lambert PF, Howes KA, Windle JJ, Lasudry JG. Transgenic models of retinoblastoma; what they tell us about its cause and treatment. Trans Am Ophthalmol Soc 1994;92:385–400.

21. Jwala J, Vadlapatla RK, Vadlapudi AD, Boddu SH, Pal D, Mitra AK. Differential expression of folate receptoralpha, sodium-dependent multivitamin transporter, and amino acid transporter (B (0, +)) in human retinoblastoma (Y-79) and retinal pigment epithelial (ARPE-19) cell lines. J Ocul Pharmacol Ther 2012;28:237–244.

22. Jez M, Bas T, Veber M, Košir A, Dominko T, Page R, et al. The hazards of DAPI photoconversion: effects of dye, mounting media and fixative, and how to minimize the problem. Histochem Cell Biol 2013;139:195–204.

23. Francis JH, Roosipu N, Levin AM, Brodie SE, Dunkel IJ, Gobin YP, et al. Current treatment of bilateral retinoblastoma: the impact of intraarterial and intravitreous chemotherapy. Neoplasia 2018;20:757–763.

24. Munier FL, Gaillard MC, Balmer A, Soliman S, Podilsky G, Moulin AP, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol 2012;96:1078– 1083.

25. Shields CL, Lally SE, Leahey AM, Jabbour PM, Caywood EH, Schwendeman R, et al. Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Curr Opin Ophthalmol 2014;25:374–385.

26. Abramson DH, Ji X, Francis JH, Catalanotti F, Brodie SE, Habib L. Intravitreal chemotherapy in retinoblastoma: expended use beyond intravitreal seeds. Br J Ophthalmol 2018; June 6 [Epub ahead of print].