Multifunctional capacity and therapeutic potential of lactoferrin

Moreno-Expósito, Luis; Illescas‐Montes, Rebeca; Melguizo‐Rodríguez, Lucia; Ruíz, Concepción; Ramos‐Torrecillas, Javier; Luna-Bertos, Elvira De

doi:10.1016/j.lfs.2018.01.002

Cited by 95 publications

(77 citation statements)

References 37 publications

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“…It has numerous clinically significant physiological functions viz., anti-inflammation, host defense against infections, maintenance of iron homeostasis, etc. [25][26][27][28]. Since brain endothelial cells, and glioblastoma cells [29][30][31][32][33] express lactoferrin receptors and also its low endogenous levels in serum [34,35], make lactoferrin more advantageous in using it for targeting to the brain as it avoids competition with endogenous ligands and also increases target specificity.…”

Section: Introductionmentioning

confidence: 99%

Carmustine Loaded Lactoferrin Nanoparticles Demonstrates an Enhanced Antiproliferative Activity Against Glioblastoma in Vitro

Athmakur

Kondapi

2018

Int J App Pharm

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Objective: Despite sophisticated treatment regimens, there is no significant improvement in the mortality rates of glioblastoma due to insufficient dosage delivery, reoccurrence of tumors, higher systemic toxicity, etc. Since brain endothelial cells and glioblastoma cells express lactoferrin receptors, a target-specific drug delivery vehicle was developed using lactoferrin itself as a matrix, into which carmustine was loaded. The objective was to use carmustine loaded lactoferrin nanoparticles (CLN) to achieve higher therapeutic efficacy and target specificity compared to free carmustine.Methods: CLN were prepared using the Sol-oil method. The nanoparticles prepared were characterized for their size, shape, polydispersity, and stability using FESEM and DLS methods. Drug loading and drug releasing efficiencies were also estimated. Further, cellular uptake of nanoparticles and their antiproliferative efficacy against glioblastoma cells were evaluated.Results: Characterization of CLN showed that they were spherical with ≤ 41 nm diameter and exhibited homogeneously dispersed stable distribution. Loading efficiency of carmustine in CLN was estimated to be 43±3.7 %. Drug release from the nanoparticles was pH dependent with the maximum observed at pH 5. At physiological and gastric pH, drug release was lower, whereas maximum release was observed at endocytotic vesicular and around tumor extracellular pH. Confocal microscopic studies showed an active cellular uptake of nanoparticles. Results of antiproliferative analysis substantiated a higher antiproliferative effect for CLN compared to free carmustine.Conclusion: The results of the study demonstrated that CLN serves as a vital tool, in designing an effective treatment strategy for targeted drug delivery to glioblastoma.

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Section: Introductionmentioning

confidence: 99%

Carmustine Loaded Lactoferrin Nanoparticles Demonstrates an Enhanced Antiproliferative Activity Against Glioblastoma in Vitro

Athmakur

Kondapi

2018

Int J App Pharm

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“…One protein of practical interest is lactoferrin (Lf), which, besides its antimicrobial and anti-carcinogenic activities, also has an anti-inflammatory function and an osteogenic role [36,37]. Lf released at the site of injury interacts with microbial elements and with cells of the immune system, affecting them at both the cellular and molecular level [38][39][40][41][42][43][44].…”

Section: Of 19mentioning

confidence: 99%

Macrophage in vitro Response on Hybrid Coatings Obtained by Matrix Assisted Pulsed Laser Evaporation

et al. 2019

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The improvement in the research area of the implant by surface functionalization when correlated with the biological response is of major interest in the biomedical field. Based on the fact that the inflammatory response is directly involved in the ultimate response of the implant within the body, it is essential to study the macrophage-material interactions. Within this context, we have investigated the composite material-macrophage cell interactions and the inflammatory response to these composites with amorphous hydroxyapatite (HA), Lactoferrin (Lf), and polyethylene glycol-polycaprolactone (PEG-PCL) copolymer. All materials are obtained by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique and characterized by Atomic Force Microscopy and Scanning Electron Microscopy. Macrophage-differentiated THP-1 cells proliferation and metabolic activity were assessed by qualitative and quantitative methods. The secretion of tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) cytokine, in the presence and absence of the inflammatory stimuli (bacterial endotoxin; lipopolysaccharide (LPS)), was measured using an ELISA assay. Our results revealed that the cellular response depended on the physical-chemical characteristics of the coatings. Copolymer-HA-Lf coatings led to low level of pro-inflammatory TNF-α, the increased level of anti-inflammatory IL-10, and the polarization of THP-1 cells towards an M2 pro-reparative phenotype in the presence of LPS. These findings could have important potential for the development of composite coatings in implant applications.

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“…Мы используем в качестве модельной системы детекцию белка лактоферрина в образце плазмы крови человека, используя ранее полученную нами пару нанотел, узнающих неперекрываю- [7]. Целью исследования в данной работе была демонстрация того, что иммуносорбенты на основе определенной комбинации однодоменных антител (нанотел), способных специфически связывать (и удалять) конкретные мажорные белки крови человека, могут быть подобраны для заданного маркерного антигена крови таким образом, что будут эффективным инструментом предобработки крови с целью уменьшения интерференции (неспецифического фонового сигнала) и повышения чувствительности при диагностическом иммуноферментном анализе.…”

Section: Institute Of Gene Biology Russian Academy Of Sciences Moscunclassified

A New Method Based on the Use of Immobilized Single-Domain Antibodies to Remove Certain Major Proteins From Blood Plasma Helps to Reduce Nonspecific Signal in an Immunoassay

et al. 2019

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A generally underestimated problem of immunoassays is its susceptibility to various interferences, being the Achilles heel of these assays (interventions in the analysis). The presence of interfering substances in the patient’s specimen can cause erroneous test sample result, which may lead to incorrect diagnosis and catastrophic consequences for the patient. Hence, one should pay particular attention to identifying possible interferences in the test systems used and, when possible, develop and apply methods to overcome them. The issue of avoiding interference is particularly important for immunoassays of biomarkers in human plasma or serum. In order to reduce possible interferences, it would be desirable to have an opportunity of specific and adaptable pretreatment of blood samples for a specifically assayed marker protein, as applied to a specific test system. We assume that such pretreatment may be done by combining the immunosorbents based on the use of special single-domain antibodies (nanobodies).The nanobodies are recombinant proteins, derivatives of single-domain antigen-recognizing variable fragments of specific antibodies, consisting of a dimer of truncated heavy chains in the complete absence of light chains. Such specific antibodies are detectable in the normal samples taken from members of the Camelidae family (Camelids), and in some species of cartilaginous fishes, along with the common antibodies. The special properties of nanobodies can provide certain advantages in their use, compared with antibodies of traditional structure and their derivatives.In this paper, we have shown for the first time, that the immunosorbents based on certain combination of single-domain antibodies used as ligands able for specifically binding and removal of specific high-abundance human blood proteins, may be selected for a given marker blood antigen in such a way that they will be an effective tool for blood pretreatment, aiming to reduce possible effects of interference and increased sensitivity in the diagnostic “sandwich” enzyme immunoassay. A new method of plasma pretreatment is demonstrated with human plasma samples (at a dilution of 1:40) of two patients. A previously developed model system for detection of lactoferrin protein was used to analyze plasma samples. It is shown that a significantly increased ratio of total detected signal to the nonspecific background signal could be obtained after drastic reduction of this background by affinity removal of 3 major protein fractions, i.e., fibrinogen, IgG alpha-2-macroglobulin from blood plasma samples, using appropriate immobilized single domain antibodies.

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Multifunctional capacity and therapeutic potential of lactoferrin

Cited by 95 publications

References 37 publications

Carmustine Loaded Lactoferrin Nanoparticles Demonstrates an Enhanced Antiproliferative Activity Against Glioblastoma in Vitro

Carmustine Loaded Lactoferrin Nanoparticles Demonstrates an Enhanced Antiproliferative Activity Against Glioblastoma in Vitro

Macrophage in vitro Response on Hybrid Coatings Obtained by Matrix Assisted Pulsed Laser Evaporation

A New Method Based on the Use of Immobilized Single-Domain Antibodies to Remove Certain Major Proteins From Blood Plasma Helps to Reduce Nonspecific Signal in an Immunoassay

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