Evaluation of the Ophthalmotoxic Effect of Quantum Dots and Bioconjugates Based on Them in Terms of the Prospects for the Treatment of Resistant Endophthalmitis. Experimental Research (Stage 1)

Endophthalmitis remains one of the most formidable complications of surgery in ophthalmology, leading to significant functional and anatomical changes. The “gold” standard of treatment for this pathology is the installation of intravenous injections of antibacterial drugs, but taking into account the number and type of pathogens, the growth of antibiotic resistance, the search for alternative methods of treatment of endophthalmitis remains relevant. Colloidal quantum dots, which are nanoscale semiconductor crystals with simulated optical and electronic properties due to changes in their volume, composition, and surface connections, are of interest for research in this direction. This article presents the process of synthesis of CT and bioconjugates based on them in order to assess ophthalmotoxicity with the prospect of further use in the treatment of endophthalmitis. The study was divided into 4 stages, starting with the determination of the required technical specification in order to select the appropriate type of quantum dots taking into account the physical and chemical characteristics (Stage 1), the synthesis of quantum dots (Stage 2), the preparation and titration of a solution of quantum dots of various concentrations for implantation in the vitreous cavity (Stage 3). The final stage was to evaluate the toxic effect of the quantum dot solution in its pure form, as well as in combination with antibiotics (ceftazidime and vancomycin) when administered intravitreally on an animal model. As a result of the study, quantum dots were synthesized and a solution based on them was obtained for introduction into the vitreous cavity. Based on the testing of the animal model (rabbits), a safe dose of the solution was determined, as well as the possibility of its use in combination with antibiotics.

1. Barry P., Cordoves L., Gardner S. ESCRS Guidelines for Prevention and Treatment of Endopthalmitis Following Cataract Surgery. Co Dublin: Temple House, Temple Road, Blackrock. 2013:1–22.

2. Sim H.E. Kang M.J. Kim J.S. Intravitreal Voriconazole for Treatment of Bilateral Endogenous Candida Chorioretinitis. Case Rep Ophthalmol. 2020;11:402–410. DOI: https://doi.org/10.1159/000508912

3. AlBloushi A., Almousa A., Alkheraiji N. Postpartum Endogenous Candida Endophthalmitis. 2019;26(2):110–113. DOI: 10.4103/meajo.MEAJO_284_18

4. Babalola O. E. Intravitreal linezolid in the management of vancomycin-resistant enterococcal endophthalmitis. Am J Ophthalmol Case Rep. 2020;20:100974. DOI: 10.1016/j.ajoc.2020.100974

5. Dave V., Pathengay A., Nishant K. Clinical presentations, risk factors and outcomes of ceftazidime-resistant Gram-negative endophthalmitis. Clinical and Experimental Ophthalmology. 2016;45(3):2–7. DOI: 10.1111/ceo.12833

6. Tereshchenko A.V., Trifanenkova I.G., Okuneva M.V. Fungal endophthalmitis. Ophthalmosurgery = Oftal’mokhirurgiya. 2019;2:70–75 (In Russ.). DOI: 10.25276/0235-4160-2019-2-70-75

7. Read A.F., Woods R.J. Antibiotic resistance management. Evol. Med. Public Health. 2014;14(1):147. DOI: 10.1093/emph/eou024

8. Tedersoo L., Sanchez-Ramirez S., Koljalg U. High-level classification of the Fungi and a tool for evolutionary ecological analyses. Fungal Diversity. 2018;90:135–159. DOI: 10.1007/s13225-018-0401-0

9. Rao N.A., Hidayat A.A. Endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared with aspergillosis. Am. J. Ophthalmol. 2001;3(2):244–251. DOI: 10.1016/s0002-9394(01)00968-0

10. No authors listed. The antibiotic alarm. Nature. 2013;495(7440):14. DOI: 10.1038/495141a

11. Viswanathan V.K. Off-label abuse of antibiotics by bacteria. Gut. Microbes. 2014;5(1):3–4. DOI: 10.4161 / gmic.28027

12. Schimel A.M., Miller D., Flynn H.W., Jr Endophthalmitis isolates and antibiotic susceptibilities: a 10-year review of culture-proven cases. Am J Ophthalmol 2013;156:50–52. DOI: 10.1016/j.ajo.2013.01.027

13. Gentile R.C., Shukla S., Shah M. Microbiological spectrum and antibiotic sensitivity in endophthalmitis: a 25-year review. Ophthalmology. 2014;121:1634–1642. DOI:10.1016/j.ophtha.2014.02.001

14. Sheng Y., Sun W., Gu Y. Endophthalmitis after cataract surgery in China, 1995–2009. J Cataract Refract Surg. 2011;37:1715–1722. DOI: 10.1016/j.jcrs.2011.06.019

15. Wong T.Y., Chee S.P. The epidemiology of acute endophthalmitis after cataract surgery in an Asian population. Ophthalmology. 2004;111:699–705. DOI: 10.1016/j.ophtha.2003.07.014

16. Alivisatos A.P. Semiconductor clusters, nanocrystals, and quantum dots. Science. 1996;271:933–937. DOI: 10.1126/science.271.5251.933

17. Weller H. Quantum size colloids: From size-dependent properties of discrete particles to self-organized superstructures. Curr. Opin. Colloid Interface Sci. 1998;3:194–199. DOI: 10.1016/S1359-0294(98)80013-7

18. Weng J., Song X., Li L. Highly luminescent CdTe quantum dots prepared in aqueous phase as an alternative fluorescent probe for cell imaging. Talanta. 2006;70:397–402. DOI: 10.1016/j.talanta.2006.02.064

19. Courtney C.M., Goodman S.M., Nagy T.A., Levy M., Bhusal P., Madinger N.E. Potentiating antibiotics in drug-resistant clinical isolates via stimuliactivated superoxide generation. Sci. Adv. 2017;3(10):1–10. DOI: 10.1126/sciadv.170177

20. Courtney C.M., Goodman S.M., McDaniel J.A., Madinger N.E., Chatterjee A., Nagpal P. Photoexcited quantum dots for killing multidrug-resistant bacteria. Nat. Mater. 2016;15:529–534. DOI: 10.1038/nmat4542

21. Wang J., Long Y., Zhang Y. Preparation of Highly Luminescent CdTe/CdS Core/Shell Quantum Dots. Chem. Phys. Chem. 2009;10:680–685. DOI: https://doi.org/10.1002/cphc.200800672

22. Jo J.H., Jo D.Y., Lee S.H. InP-Based Quantum Dots Having an InP Core, Composition-Gradient ZnSeS Inner Shell, and ZnS Outer Shell with Sharp, Bright Emissivity, and Blue Absorptivity for Display Devices. ACS Applied Nano Materials. 2020;3(2):1972–1980. DOI: 10.1021/acsanm.0c00008

23. Pong B.K., Trout B.L., LeeLangmuir J. Y. Modified Ligand-Exchange for Efficient Solubilization of CdSe/ZnS Quantum Dots in Water: A Procedure Guided by Computational Studies. 2008;24(10):5270–5276. DOI: 10.1021/la703431j

24. Sarwat S., Stapleton F., Willcox M. Quantum dots in Ophthalmology: A literature review. Current Eye Research. 2019;1037–1046. DOI: 10.1080/02713683.2019.1660793/