CREATION OF EFFECTIVE BIOCATALYTIC NANOSCAVENGERS FOR ORGANOPHOSPHORUS DETOXIFICATION: INFLUENCE OF NANOPARTICLE TYPE

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Abstract

Biocompatible nanosystems of various types containing a phosphotriesterase mutant obtained from hyperthermophilic archaea Saccharolobus solfataricus (PTE), such as: polymersomes based on amphiphilic di- and triblock copolymers of polyethylene glycol- polysulfide (PEG-PPS), liposomes and solid lipid nanoparticles can be used as biocatalytic nanoscavengers for hydrolytic detoxification of the organophosphorus compound paraoxon. The characteristics of PTE- loaded nanoparticles, determined by the dynamic light scattering are: diameter of about 100 nm, polydispersity not exceeding 0.3 and negative surface potential, indicate the possibility of their use in detoxification therapy. Determination of the concentration of polymer nanoparticles in solution by ultramicroscopy made it possible to calculate the concentration of the enzyme inside the nanoparticles, which is much higher than the concentration of the toxicant (paraoxon). Membrane permeability for the paraoxon hydrolysis product - para-nitro phenol and PTE enzyme was estimated by dialysis. The kinetic study of the paraoxon hydrolysis catalyzed by the free PTE and PTE- containing nanosystems showed that an enzyme encapsulation and a type of nanoparticles do not change the Michaelis-Menten enzyme reaction mechanism. The catalytic activity of PTE in nanosystems was found to be higher than in its non- encapsulated form and depend on the type of nanoparticles. Of the series of nanosystems studied, the most promising for further testing and detoxification therapy are polymersomes based on PEG-PPS.

About the authors

T. N Pashirova

Kazan (Volga Region) Federal University; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences

Email: tatyana_pashirova@mail.ru
Kazan, Russia

D. A Tatarinov

Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences

Kazan, Russia

M. V Gabova

Kazan (Volga Region) Federal University

Kazan, Russia

S. N Batasheva

Kazan (Volga Region) Federal University

Kazan, Russia

V. N Kuryakov

Oil and Gas Research Institute, Russian Academy of Sciences

Moscow, Russia

Z. M Shaihutdinova

Kazan (Volga Region) Federal University; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences

Kazan, Russia

V. F Mironov

Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences

Kazan, Russia

P. Masson

Kazan (Volga Region) Federal University

Kazan, Russia

References

  1. Raj A., Dubey A., Malla M.A., et al. Pesticide pestilence: Global scenario and recent advances in detection and degradation methods //Jinviron. Manage. 2023. V. 338. P. 117680. https://doi.org/10.1016/j.jenvman.2023.117680
  2. Fu H., Tan P., Wang R., et al. Advances in organophosphorus pesticides pollution: Current status and challenges in ecotoxicological, sustainable agriculture, and degradation strategies //J. Hazard. Mater. 2022. V. 424. P. 127494. https://doi.org/10.1016/j.jhazmat.2021.127494
  3. Choi S.K. Nanomaterial-enabled sensors and therapeutic platforms for reactive organophosphates // Nanomaterials. 2021. V. 11. N. 1. P. 1-23. https://doi.org/10.3390/nano11010224
  4. Yang J., Li H., Zou H., et al. Polymer nanoantidotes // Chem. - A Eur. J. 2023. V. 29. N. 42. P. e202301107. https://doi.org/10.1002/chem.202301107
  5. Kuchler A., Yoshimoto M., Luginbuhl S., et al. Enzymatic reactions in confined environments // Nature Nanotech. 2016. V. 11. P. 409-420. https://doi.org/10.1038/nnano.2016.54
  6. Wang Y., Zhao Q., Haag R., et al. Biocatalytic synthesis using self-assembled polymeric nano- and microreactors // Angew. Chemie Int. Ed. 2022. V. 61. N. 52. P. e202213974. https://doi.org/10.1002/anie.202213974
  7. Rosso A.P., de Oliveira F.A., Guegan P., et al. Evaluation of polymerome permeability as a fundamental aspect towards the development of artificial cells and nanofactories // J. Colloid Interface Sci. 2024. V. 671. P. 88-99. https://doi.org/10.1016/j.jcis.2024.05.133
  8. Zong W., Shao X., Li J., et al. Synthetic intracellular environments: From basic science to applications // Anal. Chem. 2023. V. 95. N. 1. P. 535-549. https://doi.org/10.1021/acs.analchem.2c04199
  9. Jiang W., Wu Z., Gao Z., et al. Artificial cells: Past, present and future // ACS Nano 2022. V. 16. N. 10. P. 15705-15733. https://doi.org/10.1021/acsnano.2c06104
  10. Jiang R., Nilam M., Piselli C., et al. Vesicle-encapsulated chemosensing ensembles allow monitoring of transmembrane uptake coupled with enzymatic reactions // Angew. Chemie Int. Ed. 2025. V. 64. N. 13. P. e202425157. https://doi.org/10.1002/anie.202425157
  11. Pang Z., Cao Z., Li W., et al. Superwettable interface towards biodetection in confined space // Nano Res. 2024. V. 17. P. 602-617. https://doi.org/10.1007/s12274-023-6108-x
  12. Sun Z., Hou Y. Micro/Nanorobots as active delivery systems for biomedicine: from self-propulsion to controllable navigation // Adv. Ther. 2022. V. 5. N. 7. P. 2100228. https://doi.org/10.1002/adpt.202100228
  13. Li J., Esteban-Fernández de Ávila B., Gao W., et al. Micro/nanorobots for biomedicine: Delivery, surgery, sensing, and detoxification // Sci. Robot. 2017. V. 2. N. 4. P. eaam6431. https://doi.org/10.1126/scirobotics.aam6431
  14. Peng Z., Iwabuchi S., Izumi K., et al. Lipid vesicle-based molecular robots // Lab Chip. 2024. V. 24. N. 5. P. 996-1029. https://doi.org/10.1039/D3LC00860F
  15. Gaur D., Dubey N.C., Tripathi B.P. Biocatalytic self-assembled synthetic vesicles and coacervates: From single compartment to artificial cells // Adv. Colloid Interface Sci. 2022. V. 299. P. 102566. https://doi.org/10.1016/j.cis.2021.102566
  16. Sun Q., Shi J., Sun H., et al. Membrane and lumen-compartmentalized polymersomes for biocatalysis and cell mimics // Biomacromolecules. 2023. V. 24. N. 11. P. 4587-4604. https://doi.org/10.1021/acs.biomac.3c00726
  17. Baumann P., Spulber M., Fischer O., et al. Investigation of Horseradish peroxidase kinetics in an "Organelle-like" environment // Small. 2017. V. 13. N. 17. P. 1603943. https://doi.org/10.1002/smll.201603943
  18. Chauhan K., Zirate-Romero A., Sengar P., et al. Catalytic kinetics considerations and molecular tools for the design of multienzymatic caascade nanoreactors // ChemCatChem. 2021. V. 13. N. 17. P. 3732-3748. https://doi.org/10.1002/cctc.202100604
  19. Shajathdinova Z., Pashirova T., Masson P. Kinetic processes in enzymatic nanoreactors for in vivo detoxification // Biomedicines. 2022. V. 10. N. 4. P. 784. https://doi.org/10.3390/biomedicines10040784
  20. Poirier L., Pinault L., Armstrong N., et al. Evaluation of a robust engineered enzyme towards organophosphorus insecticide bioremediation using planarians as biosensors // Chem. Biol. Interact. 2019. V. 306. P. 96-103. https://doi.org/10.1016/j.cbi.2019.04.013
  21. Rémy B., Plener L., Poirier L., et al. Harnessing hyperthermostable lactonase from Sulfolobus solfataricus for biotechnological applications // Sci. Rep. 2016. V. 6. P. 37780. https://doi.org/10.1038/srep37780
  22. Poirier L., Brun L., Jacquet P., et al. Enzymatic degradation of organophosphorus insecticides decreases toxicity in planarians and enhances survival // Sci. Rep. 2017. V. 7. P. 15194. https://doi.org/10.1038/s41598-017-15209-8
  23. Pashirova T., Shaihutdinova Z., Mansurova M., et al. Enzyme nanoreactor for in vivo detoxification of organophosphates // ACS Appl. Mater. Interfaces. 2022. V. 14. N. 17. P. 19241-19252. https://doi.org/10.1021/acsami.2c03210
  24. Pashirova T., Shaihutdinova Z., Tatarinov D., et al. Tuning the envelope structure of enzyme nanoreactors for in vivo detoxification of organophosphates // Int. J. Mol. Sci. 2023. V. 24. N. 21. P. 15756. https://doi.org/10.3390/ijms242115756
  25. Pashirova T., Shaihutdinova Z., Tatarinov D., et al. Pharmacokinetics and fate of free and encapsulated IRD800CW-labelled human BChE intravenously administered in mice // Int. J. Biol. Macromol. 2024. V. 282. P. 137305. https://doi.org/10.1016/j.ijbiomac.2024.137305
  26. O'Neil C.P., Suzuki T., Demurtas D., et al. A novel method for the encapsulation of biomolecules into polymersomes via direct hydration // Langmuir. 2009. V. 25. N. 16. P. 9025-9029. https://doi.org/10.1021/la900779t
  27. Jacquet P., Hiblot J., Daudé D., et al. Rational engineering of a native hyperthermostable lactonase into a broad spectrum phosphotriesterase // Sci. Rep. 2017. V. 7. P. 16745. https://doi.org/10.1038/s41598-017-16841-0
  28. Jacquet P., Billot R., Shimon A., et al. Changes in active site loop conformation relate to the transition toward a novel enzymatic activity // JACS Au. 2024. V. 4. N. 5. P. 1941-1953. https://doi.org/10.1021/jacsau.4c00179
  29. Kumar M., Grzelakowski M., Zilles J., et al. Highly permeable polymeric membranes based on the incorporation of the functional water channel protein Aquaporin Z // Proc. Natl. Acad. Sci. 2007. V. 104. N. 52. P. 20719-20724. https://doi.org/10.1073/pnas.0708762104
  30. Pashirova T.N., Zueva I. V., Petrov K.A., et al. Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactor 2-PAM as encapsulated drug model // Colloids Surfaces B Biointerfaces. 2018. V. 171. P. 358-367. https://doi.org/10.1016/j.colsurfb.2018.07.049
  31. Fangueiro J.F., Andreani T., Fernandes L., et al. Physicochemical characterization of epigallocatechin gallate lipid nanoparticles (EGCG-LNs) for ocular instillation // Colloids Surfaces B Biointerfaces. 2014. V. 123. P. 452-460. https://doi.org/10.1016/j.colsurfb.2014.09.042
  32. Popov K., Vainer Y., Silaev G., et al. Potential nano/microcenters of crystal nucleation in reagent-grade purity solvents and their differentiation by fluorescent-tagged antiscalant // Crystals. 2024. V. 14. N. 7. P. 650. https://doi.org/10.3390/cryst14070653
  33. Maffeis V., Skowicki M., Wolf K.M.P., et al. Advancing the design of artificial nano- organelles for targeted cellular detoxification of reactive oxygen species // Nano Lett. 2024. V. 24. N. 9. P. 2698-2704. https://doi.org/10.1021/acs.nanolett.3c03884
  34. Itel F., Chami M., Najer A., et al. Molecular organization and dynamics in polymerome membranes: lateral diffusion study // Macromolecules. 2014. V. 47. N. 21. P. 7588-7596. https://doi.org/10.1021/ma5015403
  35. Knaak J. B., Dary C. C., Power F. Physicochemical and biological data for the development of predictive organophosphorus pesticide QSARs and BPBK/PD models for human risk assessment // Crit. Rev. Toxicol. 2004. V. 34 N. 2. P. 143-207. https://doi.org/10.1080/10408440490432250
  36. Eyer F., Eyer P. Enzyme-based assay for quantification of paraoxon in blood of parathion poisoned patients // Hum Exp Toxicol. 1998. V. 17 N. 12. P. 645-651. https://doi.org/10.1177/096032719801701201
  37. Allen S.D., Liu Y.- G., Bobbala S., et al. Polymersomes scalably fabricated via flash nanoprecipitation are non-toxic in non-human primates and associate with leukocytes in the spleen and kidney following intravenous administration // Nano Res. 2018. V. 11. P. 5689-5703. https://doi.org/10.1007/s12274-018-2069-x
  38. Zhu S., Li S., Escuin-Ordinas H., et al. Accelerated wound healing by injectable star poly(ethylene glycol)- b-poly(propylene sulfide) scaffolds loaded with poorly water-soluble drugs // J. Control. Release. 2018. V. 282. P. 156-165. https://doi.org/10.1016/j.jconrel.2018.05.006
  39. Velluto D., Bojadzic D., De Toni T., et al. Drug-Integrating Amphiphilic Nanomaterial Assemblies: 1. Spatiotemporal control of cyclosporine delivery and activity using nanomicelles and nanofibrils // J. Control. Release. 2021. V. 329. P. 955-970. https://doi.org/10.1016/j.jconrel.2020.10.026
  40. Discher D.E., Eisenberg A. Polymer vesicles // Science. 2002. V. 297. N. 5583. P. 967-973. https://doi.org/10.1126/science.1074972
  41. Cerritelli S., Velluto D., Hubbell J.A., et al. PEG- SS- PPS: Reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery // Biomacromolecules. 2007. V. 8. N. 6. P. 1966-1972. https://doi.org/10.1021/bm070085x
  42. Velluto D., Demurtas D., Hubbell J.A. PEG- b- PPS diblock copolymer aggregates for hydrophobic drusolubilization and release: cyclosporin A as an example // Mol. Pharm. 2008. V. 5. N. 4. P. 632-642. https://doi.org/10.1021/mp7001297
  43. Scott E.A., Stano A., Gillard M., et al. Dendritic cell activation and T cell priming with adjuvant- and antigen- loaded oxidation- sensitive polymersomes // Biomaterials. 2012. V. 33. N. 26. P. 6211-6219. https://doi.org/10.1016/j.biomaterials.2012.04.060
  44. Luisi P.L., Souza T.P. de, Stano P. Vesicle behavior: insearch of explanations // J. Phys. Chem. B. 2008. V. 112. N. 46. P. 14655-14664. https://doi.org/10.1021/jp8028598
  45. Pashirova T.N., Bogdanov A.V., Masson P. Therapeutic nanoreactors for detoxification of xenobiotics: Concepts, challenges and biotechnological trends with special emphasis to organophosphate bioscavenging // Chem. Biol. Interact. 2021. V. 346. P. 109577. https://doi.org/10.1016/j.cbi.2021.109577
  46. Belluati A., Craciun I., Liu J., et al. Nanoscale enzymatic compartments in tandem support cascade reactions in vitro // Biomacromolecules. 2018. V. 19. N. 10. P. 4023-4033. https://doi.org/10.1021/acs.biomac.8b01019
  47. Varlas S., Foster J.C., Georgiou P.G., et al. Tuning the membrane permeability of polymersome nanoreactors developed by aqueous emulsion polymerization-induced self-assembly // Nanoscale. 2019. V. 11. № 26. P. 12643-12654. https://doi.org/10.1039/C9NR02507C
  48. Balasubramanian V., Correia A., Zhang H., et al. Biomimetic engineering using cancer cell membranes for designing compartmentalized nanoreactors with organelle-like functions // Adv. Mater. 2017. V. 29. № 11. P. 1605375. https://doi.org/10.1002/adma.201605375
  49. Chen Q., Schönherr H., Vancso G.J. Block-copolymer vesicles as nanoreactors for enzymatic reactions // Small. 2009. V. 5. № 12. P. 1436-144. https://doi.org/10.1002/smll.200801455
  50. Chen Q., Rausch K.G., Schönherr H., et al. α-Chymotrypsin-catalyzed reaction confined in block-copolymer vesicles // ChemPhysChem. 2010. V. 11. № 16. P. 3534-3540. https://doi.org/10.1002/cphc.201000429
  51. Sunami T., Hosoda K., Suzuki H., et al. Cellular compartment model for exploring the effect of the lipidic membrane on the kinetics of encapsulated biochemical reactions // Langmuir. 2010. V. 26. № 11. P. 8544-8551. https://doi.org/10.1021/la904569m

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