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Research Article

Nanotherapeutic potential of antibacterial folic acid-functionalized nanoceria for wound-healing applications

    Kunal Sarkar

    Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India

    ,
    Kaushik Dutta

    Department of Polymer Science & Technology, University of Calcutta, 92 A.P.C. Road, Kolkata, 700009, India

    ,
    Arindam Chatterjee

    Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India

    ,
    Jit Sarkar

    Department of Botany, Molecular & Applied Mycology & Plant Pathology Laboratory, University of Calcutta, Kolkata, West Bengal, 700019, India

    ,
    Dipankar Das

    Department of Allied Health Sciences, Brainware University, 398, Ramkrishnapur Road, Kolkata, West Bengal, 700125, India

    ,
    Arbind Prasad

    Department of Mechanical Engineering, Katihar Engineering College (Under Department of Science & Technology, Government of Bihar), Katihar, Bihar, 854109, India

    ,
    Dipankar Chattopadhyay

    Department of Polymer Science & Technology, University of Calcutta, 92 A.P.C. Road, Kolkata, 700009, India

    ,
    Krishnendu Acharya

    Department of Botany, Molecular & Applied Mycology & Plant Pathology Laboratory, University of Calcutta, Kolkata, West Bengal, 700019, India

    ,
    Madhusudan Das

    Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India

    ,
    Suresh K Verma

    *Author for correspondence: Tel.: +91 977 803 4159;

    E-mail Address: sureshverma22@gmail.com

    School of Biotechnology, KIIT-DU, Bhubaneswar, Odisha, 751024, India

    &
    Sriparna De

    **Author for correspondence:

    E-mail Address: sd.ah@brainwareuniversity.ac.in

    Department of Allied Health Sciences, Brainware University, 398, Ramkrishnapur Road, Kolkata, West Bengal, 700125, India

    Published Online:https://doi.org/10.2217/nnm-2022-0233

    Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10–20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.

    Plain language summary

    The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Ghobril C, Grinstaff MW. The chemistry and engineering of polymeric hydrogel adhesives for wound closure: a tutorial. Chem. Soc. Rev. 44(7), 1820–1835 (2015).
    • 2. Boateng JS, Matthews KH, Stevens HNE, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J. Pharm. Sci. 97(8), 2892–2923 (2008).
    • 3. Hamdan S, Pastar I, Drakulich S et al. Nanotechnology-driven therapeutic interventions in wound healing: potential uses and applications. ACS Cent. Sci. 3(3), 163–175 (2017).
    • 4. Li M, Guo Y, Wei Y, MacDiarmid AG, Lelkes PI. Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. Biomaterials 27(13), 2705–2715 (2006).
    • 5. Balakrishnan B, Mohanty M, Umashankar PR, Jayakrishnan A. Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials 26(32), 6335–6342 (2005). •• Detailed explanation of therapeutic hydrogel sheets.
    • 6. Vogt C, Xing Q, He W, Li B, Frost MC, Zhao F. Fabrication and characterization of a nitric oxide-releasing nanofibrous gelatin matrix. Biomacromolecules 14(8), 2521–2530 (2013).
    • 7. Luo L-J, Nguyen DD, Huang C-C, Lai J-Y. Therapeutic hydrogel sheets programmed with multistage drug delivery for effective treatment of corneal abrasion. Chem. Eng. J. 429, 132409 (2022). • Detailed explanation of therapeutic hydrogel sheets.
    • 8. Li Y-J, Wei S-C, Chu H-W et al. Poly-quercetin-based nanoVelcro as a multifunctional wound dressing for effective treatment of chronic wound infections. Chem. Eng. J. 437, 135315 (2022).
    • 9. Schubert D, Dargusch R, Raitano J, Chan SW. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem. Biophys. Res. Commun. 342(1), 86–91 (2006). • Excellent explanation of the antioxidant properties of cerium oxide.
    • 10. Chen J, Patil S, Seal S, McGinnis JF. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat. Nanotechnol. 1(2), 142–150 (2006).
    • 11. Xu C, Qu X. Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Mater. 6(3), e90 (2014).
    • 12. Lee SS, Song W, Cho M et al. Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal diameter and surface coating. ACS Nano 7(11), 9693–9703 (2013). • Excellent explanation of the antioxidant properties of cerium oxide.
    • 13. Sack M, Alili L, Karaman E et al. Combination of conventional chemotherapeutics with redox-active cerium oxide nanoparticles – a novel aspect in cancer therapy. Mol. Cancer Ther. 13(7), 1740–1749 (2014).
    • 14. Nguyen DD, Yao C-H, Lue SJ et al. Amination-mediated nano eye-drops with enhanced corneal permeability and effective burst release for acute glaucoma treatment. Chem. Eng. J. 451, 138620 (2023).
    • 15. Luo LJ, Nguyen DD, Lai JY. Harnessing the tunable cavity of nanoceria for enhancing Y-27632-mediated alleviation of ocular hypertension. Theranostics 11(11), 5447–5463 (2021).
    • 16. Nguyen DD, Lai JY. Synthesis, bioactive properties, and biomedical applications of intrinsically therapeutic nanoparticles for disease treatment. Chem. Eng. J. 435(2), 134970 (2022). •• Excellent review of nanoparticles for disease treatment.
    • 17. Atteia BMR, El-Kak AEA, Lucchesi PA, Delafontane P. Antioxidant activity of folic acid: from mechanism of action to clinical application. FASEB J. 23(Suppl. 1), 103.7 (2009).
    • 18. Joshi R, Adhikari S, Patro BS, Chattopadhyay S, Mukherjee T. Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity. Free Radic. Biol. Med. 30(12), 1390–1399 (2001).
    • 19. Bagheri M, Jahromi BM, Zamani A. Folic acid may be a potential addition to diabetic foot ulcer treatment – a hypothesis. Int. Wound J. 8(6), 658–660 (2011).
    • 20. Das S, Singh S, Dowding JM et al. The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials 33(31), 7746–7755 (2012).
    • 21. Cimini A, Dangelo B, Das S et al. Antibody-conjugated PEGylated cerium oxide nanoparticles for specific targeting of Aβ aggregates modulate neuronal survival pathways. Acta Biomater. 8(6), 2056–2067 (2012).
    • 22. Yoshioka T, Kawada K, Shimada T, Mori M. Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am. J. Obstet. Gynecol. 135(3), 372–376 (1979).
    • 23. Dey S, Paul S, Nag A et al. Iron-pulsing, a novel seed invigoration technique to enhance crop yield in rice: a journey from lab to field aiming towards sustainable agriculture. Sci. Total Environ. 769, 144671 (2021).
    • 24. Bergmeyer HU. Methods of enzymatic analysis. Int. J. Biochem. 17(1), 143 (1985).
    • 25. Huang P, Bao L, Zhang C et al. Folic acid-conjugated silica-modified gold nanorods for x-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy. Biomaterials 32(36), 9796–9809 (2011).
    • 26. Mohamed MA, Jaafar J, Ismail AF, Othman MHD, Rahman MA. Fourier transform infrared (FTIR) spectroscopy. Membr. Charact. 3–29 (2017).
    • 27. Husain S, Verma SK, Hemlata et al. Antibacterial efficacy of facile cyanobacterial silver nanoparticles inferred by antioxidant mechanism. Mater. Sci. Eng. C 122, 111888 (2021).
    • 28. Verma SK, Panda PK, Kumari P et al. Determining factors for the nano-biocompatibility of cobalt oxide nanoparticles: proximal discrepancy in intrinsic atomic interactions at differential vicinage. Green Chem. 23(9), 3439–3458 (2021).
    • 29. Patil SN, Paradeshi JS, Chaudhari PB, Mishra SJ, Chaudhari BL. Bio-therapeutic potential and cytotoxicity assessment of pectin-mediated synthesized nanostructured cerium oxide. Appl. Biochem. Biotechnol. 180(4), 638–654 (2016).
    • 30. Zeyons O, Thill A, Chauvat F et al. Direct and indirect CeO2 nanoparticles toxicity for Escherichia coli and synechocystis. Nanotoxicology 3(4), 284–295 (2009).
    • 31. He J, Meng X, Meng C et al. Layer-by-layer pirfenidone/cerium oxide nanocapsule dressing promotes wound repair and prevents scar formation. Molecules 27(6), 1830 (2022).
    • 32. Naseri-Nosar M, Farzamfar S, Sahrapeyma H et al. Cerium oxide nanoparticle-containing poly (ϵ-caprolactone)/gelatin electrospun film as a potential wound dressing material: in vitro and in vivo evaluation. Mater. Sci. Eng. C 81, 366–372 (2017).
    • 33. Mauro M, Crosera M, Monai M et al. Cerium oxide nanoparticles absorption through intact and damaged human skin. Molecules 24(20), 3759 (2019). • Details on human skin wound healing activity.
    • 34. Kornblatt AP, Nicoletti VG, Travaglia A. The neglected role of copper ions in wound healing. J. Inorg. Biochem. 161, 1–8 (2016).
    • 35. Sen CK, Khanna S, Venojarvi M et al. Copper-induced vascular endothelial growth factor expression and wound healing. Am. J. Physiol. Hear. Circ. Physiol. 282(5), 51–55 (2002).
    • 36. Nohl H. Generation of superoxide radicals as byproduct of cellular respiration. Ann. Biol. Clin. (Paris) 52(3), 199–204 (1994).
    • 37. Roy S, Khanna S, Nallu K, Hunt TK, Sen CK. Dermal wound healing is subject to redox control. Mol. Ther. 13(1), 211–220 (2006).
    • 38. Mohanty C, Das M, Sahoo SK. Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model. Mol. Pharm. 9(10), 2801–2811 (2012). • Excellent explanation of wound healing activity.
    • 39. Panchatcharam M, Miriyala S, Gayathri VS, Suguna L. Curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species. Mol. Cell. Biochem. 290(1–2), 87–96 (2006).
    • 40. Schäfer M, Werner S. Oxidative stress in normal and impaired wound repair. Pharmacol. Res. 58(2), 165–171 (2008). • Excellent explanation of the role of reactive oxygen species in wound healing activity.
    • 41. Steiling H, Munz B, Werner S, Brauchle M. Different types of ROS-scavenging enzymes are expressed during cutaneous wound repair. Exp. Cell Res. 247(2), 484–494 (1999).
    • 42. Serarslan G, Altuǧ E, Kontas T, Atik E, Avci G. Caffeic acid phenetyl ester accelerates cutaneous wound healing in a rat model and decreases oxidative stress. Clin. Exp. Dermatol. 32(6), 709–715 (2007).