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      Lactoferrin, a unique molecule with diverse therapeutical and nanotechnological applications

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          Abstract

          Lactoferrin (LF) is a naturally glycoprotein with iron-binding properties and diverse biological applications including; antiviral, anti-inflammatory, antioxidant, anti-cancer and immune stimulating effects. In addition, LF was found to be an ideal nanocarrier for some hydrophobic therapeutics because of its active targeting potential due to overexpression of its receptor on the surface of many cells. Moreover, it was proven to be a good candidate for fabrication of nanocarriers to specifically deliver drugs in case of brain tumors owing to the capability of LF to cross the blood brain barrier (BBB). Consequently, it seems to be a promising molecule with multiple applications in the field of cancer therapy and nanomedicine.

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          Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel.

          Neil Desai, Vuong Trieu, Zhiwen Yao … (2006)
          ABI-007, an albumin-bound, 130-nm particle form of paclitaxel, was developed to avoid Cremophor/ethanol-associated toxicities in Cremophor-based paclitaxel (Taxol) and to exploit albumin receptor-mediated endothelial transport. We studied the antitumor activity, intratumoral paclitaxel accumulation, and endothelial transport for ABI-007 and Cremophor-based paclitaxel. Antitumor activity and mortality were assessed in nude mice bearing human tumor xenografts [lung (H522), breast (MX-1), ovarian (SK-OV-3), prostate (PC-3), and colon (HT29)] treated with ABI-007 or Cremophor-based paclitaxel. Intratumoral paclitaxel concentrations (MX-1-tumored mice) were compared for radiolabeled ABI-007 and Cremophor-based paclitaxel. In vitro endothelial transcytosis and Cremophor inhibition of paclitaxel binding to cells and albumin was compared for ABI-007 and Cremophor-based paclitaxel. Both ABI-007 and Cremophor-based paclitaxel caused tumor regression and prolonged survival; the order of sensitivity was lung > breast congruent with ovary > prostate > colon. The LD(50) and maximum tolerated dose for ABI-007 and Cremophor-based paclitaxel were 47 and 30 mg/kg/d and 30 and 13.4 mg/kg/d, respectively. At equitoxic dose, the ABI-007-treated groups showed more complete regressions, longer time to recurrence, longer doubling time, and prolonged survival. At equal dose, tumor paclitaxel area under the curve was 33% higher for ABI-007 versus Cremophor-based paclitaxel, indicating more effective intratumoral accumulation of ABI-007. Endothelial binding and transcytosis of paclitaxel were markedly higher for ABI-007 versus Cremophor-based paclitaxel, and this difference was abrogated by a known inhibitor of endothelial gp60 receptor/caveolar transport. In addition, Cremophor was found to inhibit binding of paclitaxel to endothelial cells and albumin. Enhanced endothelial cell binding and transcytosis for ABI-007 and inhibition by Cremophor in Cremophor-based paclitaxel may account in part for the greater efficacy and intratumor delivery of ABI-007.
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            Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - A Review (Part 1)

            F R Zahir, S Honary (2013)
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              Lactoferrin: structure, function and applications.

              Luis Gonzalez, S Arevalo Vasquez, Quintín Rascón-Cruz (2009)
              Lactoferrin (LF) is an 80 kDa iron-binding glycoprotein of the transferrin family that is expressed in most biological fluids and is a major component of the mammalian innate immune system. Its protective effects range from direct antimicrobial activities against a large panel of microorganisms, including bacteria, viruses, fungi and parasites, to anti-inflammatory and anticancer activities. These extensive activities are made possible by mechanisms of action utilising not only the capacity of LF to bind iron but also interactions of LF with molecular and cellular components of both host and pathogens. This review summarises the putative antimicrobial mechanisms, clinical applications and heterologous expression models for LF.
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                Author and article information

                Contributors
                Sally Sabra
                Mona M. Agwa
                Journal
                Journal ID (nlm-ta): Int J Biol Macromol
                Journal ID (iso-abbrev): Int. J. Biol. Macromol
                Title: International Journal of Biological Macromolecules
                Publisher: Elsevier B.V.
                ISSN (Print): 0141-8130
                ISSN (Electronic): 1879-0003
                Publication date PMC-release: 22 July 2020
                Publication date (Electronic): 22 July 2020
                Affiliations
                [a ]Department of Biotechnology, Institute of Graduate studies and Research, Alexandria University, Alexandria 21526, Egypt
                [b ]Department of Chemistry of Natural and Microbial Products, Pharmaceutical and Drug Industries Research Division, National Research Centre, 33 El-Behooth St, Dokki, Giza 12311, Egypt
                Author notes
                Article
                Publisher ID: S0141-8130(20)33926-X
                DOI: 10.1016/j.ijbiomac.2020.07.167
                PMC ID: 7374128
                PubMed ID: 32707283
                SO-VID: 8df839f4-9b8f-4de4-a8ac-8bc87f20463e
                Copyright © © 2020 Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 1 May 2020
                Date revision received : 10 July 2020
                Date accepted : 15 July 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Biochemistry
                Keywords: lactoferrin,anti-inflammatory,anti-cancer,nanoparticles,micelles,glioma
                Data availability:
                ScienceOpen disciplines: Biochemistry
                Keywords: lactoferrin, anti-inflammatory, anti-cancer, nanoparticles, micelles, glioma

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