Review Nanoformulation of lactoferrin potentiates its activity and enhances novel biotechnological applications Esmail M. El-Fakharany Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technology Applications (SRTA-City), New Borg EL-Arab 21934, Alexandria, Egypt abstract article info Article history: Received 9 July 2020 Received in revised form 23 September 2020 Accepted 24 September 2020 Available online 01 October 2020 Keywords: Lactoferrin Nanoformulation Biological activity Lactoferrin is a glycoprotein with a molecular weight of 80 kDa, which produced in many mammalian excretions. LF is involved in various physiological processes and known to possess prominent biocidal activities, serving as an effective agent against a wide range of pathogens. This effective biocidal activity of LF in association with immune system response has made this protein an attractive therapeutic candidate. Interaction of proteins with nanopar- ticles (NPs) gives rise to the formation of a dynamic NP-protein complex and can induce conformational changes in the adsorbed proteins which may lead to the change in their function. With the recent advances in nanotech- nology, NPs may provide the protection and stabilization of LF from hydrolysis by some proteases and increase their uptake by targeted cells. These nanoformulations of LF can be used as diagnosis, disease targeting and drug delivery tools. Owing to its multiple functionalities, LF is a promising active ingredient to be loaded or adsorbed to NPs for preparing a stable, controlled surface NPs. Thus, LF NPs can potentially empower the resulting nanocomplex with attracting functionalities and might be useful in many applications, e.g., to modify the optical or rheological properties of products, or to encapsulate and deliver bioactive ingredients. © 2020 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 971 2. Lactoferrin origin and structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 971 3. Functions displayed by lactoferrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 971 4. Antiviral mechanisms of lactoferrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 972 5. Anticancer activity of lactoferrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 973 6. Therapeutic properties of nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 974 7. Nanoparticles effects on the protein structure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 974 8. Nanoformulation of lactoferrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 975 9. Lactoferrin nanoformulations targeting brain cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 977 10. Glioma treatment using lactoferrin nanoformulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 978 11. Action of nanoformulated lactoferrin dependent on cellular localization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 978 12. Melanoma treatment using lactoferrin nanoformulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 978 13. Edema treatment using lactoferrin nanoformulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 978 14. Nanoformulation of lactoferrin for imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 978 15. Nanoformulation of LF for magnetic resonance imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 16. Nanoformulation of LF for food industry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 17. Conclusion and future prospective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981 International Journal of Biological Macromolecules 165 (2020) 970–984 E-mail address: esmailelfakharany@yahoo.co.uk. https://doi.org/10.1016/j.ijbiomac.2020.09.235 0141-8130/© 2020 Elsevier B.V. All rights reserved. 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