Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

A Review of the Use of Metallic Nanoparticles as a Novel Approach for Overcoming the Stability Challenges of Blood Products: A Narrative Review from 2011-2021

Author(s): Tahereh Zadeh Mehrizi*, Mehdi Shafiee Ardestani and Sedigheh Amini Kafiabad

Volume 20, Issue 3, 2023

Published on: 10 June, 2022

Page: [261 - 280] Pages: 20

DOI: 10.2174/1567201819666220513092020

Price: $65

Open Access Journals Promotions 2
Abstract

Purpose: To obtain safe and qualified blood products (e.g., platelets, plasma, and red blood cells), various limitations such as limited shelf life (especially for platelets) and stability must be addressed. In this review study, the most commonly used metal nanomaterials (e.g., gold, silver, iron, and magnetic) reported in the literature from 2011 to 2021 were discussed owing to their unique properties, which provide exciting approaches to overcome these limitations and improve the stability, safety, and quality of blood products.

Novelty: This study reviews for the first time the results of studies (from 2011 to 2021) that consider the effects of various metallic nanoparticles on the different blood products.

Results: The results of this review study showed that some metallic nanoparticles are effective in improving the stability of plasma proteins. For this purpose, modified Fe3O4 magnetic nanoparticles and citrate-AuNPs protect albumin products against stressful situations. Also, SiO2 microspheres and silicacoated magnetite nanoparticles are highly capable of improving IgG stability. ZnO nanoparticles also reduced thrombin production, and protein-coated GMNP nanoparticles prevented unwanted leakage of factor VIII through blood vessels. Furthermore, the stability and longevity of erythrocytes can be improved by AuNP nanoparticles and Zr-based organic nanoparticles. In addition, platelet storage time can be improved using PEGylated Au and functionalized iron oxide nanoparticles.

Suggestion: According to the results of this study, it is suggested that further research should be conducted on metal nanoparticles as the most promising candidates to prepare metal nanoparticles with improved properties to increase the stability of various blood products.

Keywords: RBCs, plasma, metallic nanomaterials, stability, leakage, storage.

« Previous Next »
Graphical Abstract

[1]
Love, S.A.; Thompson, J.W.; Haynes, C.L. Development of screening assays for nanoparticle toxicity assessment in human blood: Preliminary studies with charged Au nanoparticles. Nanomedicine (Lond.), 2012, 7(9), 1355-1364.
[http://dx.doi.org/10.2217/nnm.12.17] [PMID: 22583573]
[2]
Sen Gupta, A. Bio-inspired nanomedicine strategies for artificial blood components. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2017, 9(6), e1464.
[http://dx.doi.org/10.1002/wnan.1464] [PMID: 28296287]
[3]
Burnouf, T.; Radosevich, M. Affinity chromatography in the industrial purification of plasma proteins for therapeutic use. J. Biochem. Biophys. Methods, 2001, 49(1-3), 575-586.
[http://dx.doi.org/10.1016/S0165-022X(01)00221-4] [PMID: 11694303]
[4]
Evtushenko, M.; Wang, K.; Stokes, H.W.; Nair, H. Blood protein purification and simultaneous removal of nonenveloped viruses using tangential-flow preparative electrophoresis. Electrophoresis, 2005, 26(1), 28-34.
[http://dx.doi.org/10.1002/elps.200406150] [PMID: 15624167]
[5]
Belousov, A. Nanotechnology and discovery of a new factor which influences on permeability of erythrocytes and eryptosis. J. Mar. Sci. Eng., 2014, 4(11), 367-372.
[6]
Aurich, K.; Fregin, B.; Palankar, R.; Wesche, J.; Hartwich, O.; Biedenweg, D.; Nguyen, T-H.; Greinacher, A.; Otto, O. Label-free on chip quality assessment of cellular blood products using realtime deformability cytometry. Lab Chip, 2020, 20(13), 2306-2316.
[http://dx.doi.org/10.1039/D0LC00258E] [PMID: 32458864]
[7]
Pulimood, T.B.; Park, G.R. Debate: Albumin administration should be avoided in the critically ill. Crit. Care, 2000, 4(3), 151-155.
[http://dx.doi.org/10.1186/cc688] [PMID: 11211856]
[8]
Zadeh, M.T.; Mosaffa, N.; Shafiee, A.M.; Khamesipour, A.; Ebrahimi, S.H.; Pirali, H.M.; Mardani, D.Y.; Ramezani, A. In vivo therapeutic effects of four synthesized antileishmanial nanodrugs in the treatment of Leishmaniasis. Arch. Clin. Infect. Dis., 2018, 13(5), e80314.
[http://dx.doi.org/10.5812/archcid.80314]
[9]
Mehrizi, T.Z.; Ardestani, M.S.; Molla Hoseini, M.H.; Khamesipour, A.; Mosaffa, N.; Ramezani, A. Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania major. Nanomedicine (Lond.), 2018, 13(24), 3129-3147.
[http://dx.doi.org/10.2217/nnm-2018-0063] [PMID: 30463469]
[10]
Mehrizi, T.Z.; Ardestani, M.S.; Hoseini, M.H.M.; Khamesipour, A.; Mosaffa, N.; Ramezani, A. Novel nanosized chitosan-betulinic acid against resistant Leishmania major and first clinical observation of such parasite in kidney. Sci. Rep., 2018, 8(1), 1-19.
[PMID: 29311619]
[11]
Zadeh, M.T.; Pirali, H.M.; Ebrahimi, S.H.; Mirzaei, M.; Shafiee, A.M.; Haji, M.H.M.; Mosaffa, N.; Khamesipour, A.; Javanmard, A.; Rezazadeh, S.; Ramezani, A. Effective materials of medicinal plants for leishmania treatment in vivo environment. Faslnamah-i Giyahan-i Daruyi, 2020, 19(74), 39-62.
[http://dx.doi.org/10.29252/jmp.19.74.39]
[12]
Mehrizi, T.Z.; Ardestani, M.S.; Khamesipour, A.; Hoseini, M.H.M.; Mosaffa, N.; Anissian, A.; Ramezani, A. Reduction toxicity of Amphotericin B through loading into a novel nanoformulation of anionic linear globular dendrimer for improve treatment of Leishmania major. J. Mater. Sci. Mater. Med., 2018, 29(8), 125.
[http://dx.doi.org/10.1007/s10856-018-6122-9] [PMID: 30056571]
[13]
Zadeh, M.T.; Khamesipour, A.; Shafiee, A.M.; Ebrahimi, S.H.; Haji, M.H.M.; Mosaffa, N.; Ramezani, A. Comparative analysis between four model nanoformulations of amphotericin B-chitosan, amphotericin B-dendrimer, betulinic acid-chitosan and betulinic acid-dendrimer for treatment of Leishmania major: Real-time PCR assay plus. Int. J. Nanomedicine, 2019, 14, 7593-7607.
[http://dx.doi.org/10.2147/IJN.S220410] [PMID: 31802863]
[14]
Fatemeh, D.R.A.; Ebrahimi, S.H.; Abedi, A.; Alavi, S.E.; Movahedi, F.; Koohi, M.E.M.; Zadeh, M.T.; Akbarzadeh, A. Polybutylcyanoacrylate nanoparticles and drugs of the platinum family: Last status. Indian J. Clin. Biochem., 2014, 29(3), 333-338.
[http://dx.doi.org/10.1007/s12291-013-0364-6] [PMID: 24966482]
[15]
Shahabi, J.; Shahmabadi, H.E.; Alavi, S.E.; Movahedi, F.; Esfahani, M.K.M.; Mehrizi, T.Z.; Akbarzadeh, A. Effect of gold nanoparticles on properties of nanoliposomal hydroxyurea: An in vitro study. Indian J. Clin. Biochem., 2014, 29(3), 315-320.
[http://dx.doi.org/10.1007/s12291-013-0355-7] [PMID: 24966479]
[16]
Mehrizi, T.Z.; Mosaffa, N.; Khamesipour, A.; Hoseini, M.H.M.; Shahmabadi, H.E.; Ardestani, M.S.; Ramezani, A. A novel nanoformulation for reducing the toxicity and increasing the efficacy of betulinic acid using anionic linear globular dendrimer. J. Nanostruct., 2021, 11(1), 143-152.
[17]
Mehrizi, T.Z.; Rezayat, S.M.; Ardestani, M.S.; Shahmabadi, H.E.; Ramezani, A. A review study about the effect of chitosan nanocarrier on improving the efficacy of amphotericin b in the treatment of leishmania from 2010 to 2020. Curr. Drug Deliv., 2021, 18(9), 1234-1243.
[http://dx.doi.org/10.2174/1567201818666210316111941] [PMID: 33726648]
[18]
Zadeh, M.T.; Amini, K.S. Evaluation of the effects of nanoparticles on the therapeutic function of platelet: A review. J. Pharm. Pharmacol., 2022, 74(2), 179-190.
[PMID: 34244798]
[19]
Mehrizi, T.Z.; Eshghi, P. Investigation of the effect of nanoparticles on platelet storage duration 2010–2020. Int. Nano Lett., 2022, 12(1), 15-45.
[20]
Mehrizi, T.Z.; Hosseini, K.M. An overview on investigation of nanomaterials’ effect on plasma components: Immunoglobulins and coagulant factor VIII, 2010-2020 review. Nanoscale Adv., 2021, 3, 3730-3745.
[21]
Gumus, A.; Mandal, S.; Erickson, D. Particle manipulation and biosensor applications using optofluidic ring resonators. In: 6th Nanoscience and Nanotechnology Conference, 2010 Jun 15-18; Izmir, Turkey
[22]
Mehrizi, T.Z. Hemocompatibility and hemolytic effects of functionalized nanoparticles on red blood cells: A recent review study. Nano, 2021, 16(08), 2130007.
[http://dx.doi.org/10.1142/S1793292021300073]
[23]
Klein, H.G. Pathogen inactivation technology: Cleansing the blood supply. J. Intern. Med., 2005, 257(3), 224-237.
[http://dx.doi.org/10.1111/j.1365-2796.2005.01451.x] [PMID: 15715679]
[24]
He, W.J.; Hosseinkhani, H.; Hong, P.D.; Chiang, C.H.; Yu, D.S. Magnetic nanoparticles for imaging technology. Int. J. Nanotechnol., 2013, 10(10-11), 930-944.
[http://dx.doi.org/10.1504/IJNT.2013.058120]
[25]
Mottaghitalab, F.; Farokhi, M.; Shokrgozar, M.A.; Atyabi, F.; Hosseinkhani, H. Silk fibroin nanoparticle as a novel drug delivery system. J. Control. Release, 2015, 206, 161-176.
[http://dx.doi.org/10.1016/j.jconrel.2015.03.020] [PMID: 25797561]
[26]
Mahmoudi, M.; Hosseinkhani, H.; Hosseinkhani, M.; Boutry, S.; Simchi, A.; Journeay, W.S.; Subramani, K.; Laurent, S. Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. Chem. Rev., 2011, 111(2), 253-280.
[http://dx.doi.org/10.1021/cr1001832] [PMID: 21077606]
[27]
Alibolandi, M.; Abnous, K.; Sadeghi, F.; Hosseinkhani, H.; Ramezani, M.; Hadizadeh, F. Folate receptor-targeted multimodal polymersomes for delivery of quantum dots and doxorubicin to breast adenocarcinoma: in vitro and in vivo evaluation. Int. J. Pharm., 2016, 500(1-2), 162-178.
[http://dx.doi.org/10.1016/j.ijpharm.2016.01.040] [PMID: 26802496]
[28]
Mohammad-Taheri, M.; Vasheghani-Farahani, E.; Hosseinkhani, H.; Shojaosadati, S.A.; Soleimani, M. Fabrication and characterization of a new MRI contrast agent based on a magnetic dextran–spermine nanoparticle system. Iran. Polym. J., 2012, 21(4), 239-251.
[http://dx.doi.org/10.1007/s13726-012-0027-0]
[29]
Sobot, D.; Mura, S.; Couvreur, P. Nanoparticles: Blood components interactions. In: Encyclopedia of Polymeric Nanomaterials; Müllen, K.; Kobayashi, S., Eds.; Springer: Berlin, Heidelberg, 2014; pp. 1-10.
[30]
Kottana, R.K.; Maurizi, L.; Schnoor, B.; Morris, K.; Webb, J.A.; Massiah, M.A.; Millot, N.; Papa, A.L. Anti-platelet effect induced by iron oxide nanoparticles: Correlation with conformational change in fibrinogen. Small, 2021, 17(1), e2004945.
[http://dx.doi.org/10.1002/smll.202004945] [PMID: 33284518]
[31]
Babu, E.P.; Subastri, A.; Suyavaran, A.; Premkumar, K.; Sujatha, V.; Aristatile, B.; Alshammari, G.M.; Dharuman, V.; Thirunavukkarasu, C. Size dependent uptake and hemolytic effect of zinc oxide nanoparticles on erythrocytes and biomedical potential of ZnO-ferulic acid conjugates. Sci. Rep., 2017, 7(1), 1-12.
[PMID: 28127051]
[32]
Schröfel, A.; Kratošová, G.; Šafařík, I.; Šafaříková, M.; Raška, I.; Shor, L.M. Applications of biosynthesized metallic nanoparticles - a review. Acta Biomater., 2014, 10(10), 4023-4042.
[http://dx.doi.org/10.1016/j.actbio.2014.05.022] [PMID: 24925045]
[33]
Kopac, T. Protein corona, understanding the nanoparticle-protein interactions and future perspectives: A critical review. Int. J. Biol. Macromol., 2021, 169, 290-301.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.12.108] [PMID: 33340622]
[34]
Soddu, L.; Trinh, D.N.; Dunne, E.; Kenny, D.; Bernardini, G.; Kokalari, I.; Marucco, A.; Monopoli, M.P.; Fenoglio, I. Identification of physicochemical properties that modulate nanoparticle aggregation in blood. Beilstein J. Nanotechnol., 2020, 11(1), 550-567.
[http://dx.doi.org/10.3762/bjnano.11.44] [PMID: 32280579]
[35]
Kopac, T.; Bozgeyik, K. Equilibrium, kinetics, and thermodynamics of bovine serum albumin adsorption on single-walled carbon nanotubes. Chem. Eng. Commun., 2016, 203(9), 1198-1206.
[http://dx.doi.org/10.1080/00986445.2016.1160225]
[36]
Kopac, T.; Bozgeyik, K. Effect of surface area enhancement on the adsorption of Bovine Serum Albumin onto titanium dioxide. Colloids Surf. B Biointerfaces, 2010, 76(1), 265-271.
[http://dx.doi.org/10.1016/j.colsurfb.2009.11.002] [PMID: 20005083]
[37]
Kopac, T.; Bozgeyik, K.; Flahaut, E. Adsorption and interactions of the bovine serum albumin-double walled carbon nanotube system. J. Mol. Liq., 2018, 252, 1-8.
[http://dx.doi.org/10.1016/j.molliq.2017.12.100]
[38]
Bozgeyik, K.; Kopac, T. Adsorption properties of arc produced multi walled carbon nanotubes for bovine serum Albumin. Int. J. Chem. React. Eng., 2016, 14(2), 549-558.
[http://dx.doi.org/10.1515/ijcre-2015-0160]
[39]
Sen, T.; Mandal, S.; Haldar, S.; Chattopadhyay, K.; Patra, A. Interaction of gold nanoparticle with human serum albumin (HSA) protein using surface energy transfer. J. Phys. Chem. C, 2011, 115(49), 24037-24044.
[http://dx.doi.org/10.1021/jp207374g]
[40]
Anbouhi, T.S.; Esfidvajani, E.M.; Nemati, F.; Haghighat, S.; Sari, S.; Attar, F.; Pakaghideh, A.; Sohrabi, M.J.; Mousavi, S.E.; Falahati, M. Albumin binding, anticancer and antibacterial properties of synthesized zero valent iron nanoparticles. Int. J. Nanomedicine, 2018, 14, 243-256.
[http://dx.doi.org/10.2147/IJN.S188497] [PMID: 30643404]
[41]
Calzolai, L.; Laera, S.; Ceccone, G.; Gilliland, D.; Hussain, R.; Siligardi, G.; Rossi, F. Gold nanoparticles’ blocking effect on UV-induced damage to human serum albumin. J. Nanopart. Res., 2013, 15(1), 1-5.
[http://dx.doi.org/10.1007/s11051-012-1412-5]
[42]
Laera, S.; Ceccone, G.; Rossi, F.; Gilliland, D.; Hussain, R.; Siligardi, G.; Calzolai, L. Measuring protein structure and stability of protein-nanoparticle systems with synchrotron radiation circular dichroism. Nano Lett., 2011, 11(10), 4480-4484.
[http://dx.doi.org/10.1021/nl202909s] [PMID: 21932791]
[43]
Shao, Q.; Hall, C.K. Allosteric effects of gold nanoparticles on human serum albumin. Nanoscale, 2017, 9(1), 380-390.
[http://dx.doi.org/10.1039/C6NR07665C] [PMID: 27924337]
[44]
Das, S.; Purkayastha, P. Gold nanocluster protection of protein from UVC radiation: A model study on bovine serum albumin. ACS Omega, 2017, 2(6), 2451-2458.
[http://dx.doi.org/10.1021/acsomega.7b00302] [PMID: 31457592]
[45]
Capomaccio, R.; Osório, I.; Ojea-Jiménez, I.; Ceccone, G.; Colpo, P.; Gilliland, D.; Hussain, R.; Siligardi, G.; Rossi, F.; Ricard-Blum, S. Gold nanoparticles increases UV and thermal stability of human serum albumin. Biointerphases, 2016, 11(4), 04B310.
[http://dx.doi.org/10.1116/1.4972113]
[46]
Alex, S.A.; Chakraborty, D.; Chandrasekaran, N.; Mukherjee, A. A comprehensive investigation of the differential interaction of human serum albumin with gold nanoparticles based on the variation in morphology and surface functionalization. RSC Adv., 2016, 6(58), 52683-52694.
[http://dx.doi.org/10.1039/C6RA10506H]
[47]
Maji, A.; Beg, M.; Das, S.; Sahoo, N.K.; Jha, P.K.; Islam, M.M.; Hossain, M. Binding interaction study on human serum albumin with bactericidal gold nanoparticles synthesized from a leaf extract of Musa balbisiana: A multispectroscopic approach. Luminescence, 2019, 34(6), 563-575.
[http://dx.doi.org/10.1002/bio.3639] [PMID: 31044511]
[48]
Xue, J.-J.; Chen, Q.-Y. The interaction between ionic liquids modified magnetic nanoparticles and bovine serum albumin and the cytotoxicity to HepG-2 cells. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2014, 120, 161-166.
[http://dx.doi.org/10.1016/j.saa.2013.10.005] [PMID: 24184619]
[49]
Joseph, D.; Sachar, S.; Kishore, N.; Chandra, S. Mechanistic insights into the interactions of magnetic nanoparticles with bovine serum albumin in presence of surfactants. Colloids Surf. B Biointerfaces, 2015, 135, 596-603.
[http://dx.doi.org/10.1016/j.colsurfb.2015.08.022] [PMID: 26322473]
[50]
Sen, S.; Konar, S.; Pathak, A.; Dasgupta, S.; DasGupta, S. Effect of functionalized magnetic MnFe2O4 nanoparticles on fibrillation of human serum albumin. J. Phys. Chem. B, 2014, 118(40), 11667-11676.
[http://dx.doi.org/10.1021/jp507902y] [PMID: 25247718]
[51]
Chilom, C.G.; Bălan, A.; Sandu, N.; Bălăşoiu, M.; Stolyar, S.; Orelovich, O. Exploring the conformation and thermal stability of human serum albumin corona of ferrihydrite nanoparticles. Int. J. Mol. Sci., 2020, 21(24), 9734.
[http://dx.doi.org/10.3390/ijms21249734] [PMID: 33419335]
[52]
Ortiz-Dosal, A.; Loredo-García, E.; Álvarez-Contreras, A. G.; Núñez-Leyva, J. M.; Ortiz-Dosal, L. C.; Kolosovas-Machuca, E. S. Determination of the immunoglobulin g spectrum by surfaceenhanced Raman spectroscopy using Quasispherical gold nanoparticles. J. Nanomater., 2021, 2021
[http://dx.doi.org/10.1155/2021/8874193]
[53]
Magalhães, F.F.; Almeida, M.R.; Soares, S.F.; Trindade, T.; Freire, M.G.; Daniel-da-Silva, A.L.; Tavares, A.P.M. Recovery of immunoglobulin G from rabbit serum using κ-carrageenan-modified hybrid magnetic nanoparticles. Int. J. Biol. Macromol., 2020, 150, 914-921.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.135] [PMID: 32068054]
[54]
Padwal, P.; Finger, C.; Fraga-García, P.; Kaveh-Baghbaderani, Y.; Schwaminger, S.P.; Berensmeier, S. Seeking innovative affinity approaches: A performance comparison between magnetic nanoparticle agglomerates and chromatography resins for antibody recovery. ACS Appl. Mater. Interfaces, 2020, 12(36), 39967-39978.
[http://dx.doi.org/10.1021/acsami.0c05007] [PMID: 32786242]
[55]
Borlido, L.; Moura, L.; Azevedo, A.M.; Roque, A.C.; Aires-Barros, M.R.; Farinha, J.P.S. Stimuli-responsive magnetic nanoparticles for monoclonal antibody purification. Biotechnol. J., 2013, 8(6), 709-717.
[http://dx.doi.org/10.1002/biot.201200329] [PMID: 23420794]
[56]
Sotnikov, D.V.; Safenkova, I.V.; Zherdev, A.V.; Avdienko, V.G.; Kozlova, I.V.; Babayan, S.S.; Gergert, V.Y.; Dzantiev, B.B. A mechanism of gold nanoparticle aggregation by immunoglobulin G preparation. Appl. Sci. (Basel), 2020, 10(2), 475.
[http://dx.doi.org/10.3390/app10020475]
[57]
Busch, R.T.; Karim, F.; Weis, J.; Sun, Y.; Zhao, C.; Vasquez, E.S. Optimization and structural stability of gold nanoparticle–antibody bioconjugates. ACS Omega, 2019, 4(12), 15269-15279.
[http://dx.doi.org/10.1021/acsomega.9b02276] [PMID: 31552374]
[58]
Bychkova, A.V.; Lopukhova, M.V.; Wasserman, L.A.; Pronkin, P.G.; Degtyarev, Y.N.; Shalupov, A.I.; Vasilyeva, A.D.; Yurina, L.V.; Kovarski, A.L.; Kononikhin, A.S.; Nikolaev, E.N. Interaction between immunoglobulin G and peroxidase-like iron oxide nanoparticles: Physicochemical and structural features of the protein. Biochim. Biophys. Acta. Proteins Proteomics, 2020, 1868(1), 140300.
[http://dx.doi.org/10.1016/j.bbapap.2019.140300] [PMID: 31676449]
[59]
Gagnon, P.; Toh, P.; Lee, J. High productivity purification of immunoglobulin G monoclonal antibodies on starch-coated magnetic nanoparticles by steric exclusion of polyethylene glycol. J. Chromatogr. A, 2014, 1324, 171-180.
[http://dx.doi.org/10.1016/j.chroma.2013.11.039] [PMID: 24315125]
[60]
Salimi, K.; Usta, D.D.; Koçer, İ.; Çelik, E.; Tuncel, A. Protein A and protein A/G coupled magnetic SiO2 microspheres for affinity purification of immunoglobulin G. Int. J. Biol. Macromol., 2018, 111, 178-185.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.019] [PMID: 29309863]
[61]
Kaveh-Baghbaderani, Y.; Allgayer, R.; Schwaminger, S.P.; Fraga-García, P.; Berensmeier, S. Magnetic separation of antibodies with high binding capacity by site-directed immobilization of protein A-domains to bare iron oxide nanoparticles. ACS Appl. Nano Mater., 2021, 4(5), 4956-4963.
[http://dx.doi.org/10.1021/acsanm.1c00487]
[62]
Sharafi, Z.; Ranjbari, J.; Javidi, J.; Nafissi-Varcheh, N.; Tabarzad, M. Direct immobilization of coagulation factor VIII on Au/Fe3O4 shell/core magnetic nanoparticles for analytical application. Trends Pept. Protein Sci., 2016, 1(1), 20-26.
[63]
Zarabi, M.F.; Farhangi, A.; Mazdeh, S.K.; Ansarian, Z.; Zare, D.; Mehrabi, M.R.; Akbarzadeh, A. Synthesis of gold nanoparticles coated with aspartic acid and their conjugation with FVIII protein and FVIII antibody. Indian J. Clin. Biochem., 2014, 29(2), 154-160.
[http://dx.doi.org/10.1007/s12291-013-0323-2] [PMID: 24757296]
[64]
Tabarzad, M.; Sharafi, Z.; Javidi, J. Covalent immobilization of coagulation factor VIII on magnetic nanoparticles for aptamer development. J. Appl. Biomater. Funct. Mater., 2018, 16(3), 161-170.
[http://dx.doi.org/10.1177/2280800018765046] [PMID: 29609491]
[65]
Hante, N.K.; Medina, C.; Santos-Martinez, M.J. Effect on platelet function of metal-based nanoparticles developed for medical applications. Front. Cardiovasc. Med., 2019, 6, 139.
[http://dx.doi.org/10.3389/fcvm.2019.00139] [PMID: 31620449]
[66]
Yang, J-Y.; Bae, J.; Jung, A.; Park, S.; Chung, S.; Seok, J.; Roh, H.; Han, Y.; Oh, J.-M.; Sohn, S.; Jeong, J.; Cho, W.-S. Surface functionalization-specific binding of coagulation factors by zinc oxide nanoparticles delays coagulation time and reduces thrombin generation potential in vitro. PLoS One, 2017, 12(7), e0181634.
[http://dx.doi.org/10.1371/journal.pone.0181634] [PMID: 28723962]
[67]
Zhao, X.; Lu, D.; Liu, Q.S.; Li, Y.; Feng, R.; Hao, F.; Qu, G.; Zhou, Q.; Jiang, G. Hematological effects of gold nanorods on erythrocytes: Hemolysis and hemoglobin conformational and functional changes. Adv. Sci. (Weinh.), 2017, 4(12), 1700296.
[http://dx.doi.org/10.1002/advs.201700296] [PMID: 29270341]
[68]
Belousov, A.; Malygon, E.; Yavorskiy, V.; Belousova, E. Application of the standardized form Magnetite Nanoparticles (ICNB) in creature simple and practical method of additive modernization of preservation solutions for red blood cells. GJAPM, 2018, 1(3), 1-7.
[http://dx.doi.org/10.32474/GJAPM.2018.01.000101]
[69]
Rzigalinski, B.A.; Giovinco, H.M.; Cheatham, B.J. Cerium oxide nanoparticles improve lifespan of stored blood. Mil. Med., 2020, 185(Suppl. 1), 103-109.
[http://dx.doi.org/10.1093/milmed/usz210] [PMID: 32074312]
[70]
Wadhwa, R.; Aggarwal, T.; Thapliyal, N.; Kumar, A.; Yadav, P.; Kumari, V.; Reddy, B. S. C.; Chandra, P.; Maurya, P. K. Red blood cells as an efficient in vitro model for evaluating the efficacy of metallic nanoparticles. 3 Biotech, 2019, 9(7), 1-15.
[71]
Barkur, S.; Lukose, J.; Chidangil, S. Probing nanoparticle-cell interaction using micro-raman spectroscopy: Silver and gold nanoparticle-induced stress effects on optically trapped live red blood cells. ACS Omega, 2020, 5(3), 1439-1447.
[http://dx.doi.org/10.1021/acsomega.9b02988] [PMID: 32010816]
[72]
Beurton, J.; Lavalle, P.; Pallotta, A.; Chaigneau, T.; Clarot, I.; Boudier, A. Design of surface ligands for blood compatible gold nanoparticles: Effect of charge and binding energy. Int. J. Pharm., 2020, 580, 119244.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119244] [PMID: 32201250]
[73]
Purohit, R.; Vallabani, N.S.; Shukla, R.K.; Kumar, A.; Singh, S. Effect of gold nanoparticle size and surface coating on human red blood cells. Bioinspired. Biomimetic Nanobiomaterials, 2016, 5(3), 121-131.
[http://dx.doi.org/10.1680/jbibn.15.00018]
[74]
Aseichev, A.V.; Azizova, O.A.; Beckman, E.M.; Skotnikova, O.I.; Dudnik, L.B.; Shcheglovitova, O.N.; Sergienko, V.I. Effects of gold nanoparticles on erythrocyte hemolysis. Bull. Exp. Biol. Med., 2014, 156(4), 495-498.
[http://dx.doi.org/10.1007/s10517-014-2383-6] [PMID: 24771436]
[75]
Jain, V.; Kumar, H.; Anod, H.V.; Chand, P.; Gupta, N.V.; Dey, S.; Kesharwani, S.S. A review of nanotechnology-based approaches for breast cancer and triple-negative breast cancer. J. Control. Release, 2020, 326, 628-647.
[http://dx.doi.org/10.1016/j.jconrel.2020.07.003] [PMID: 32653502]
[76]
Lau, I.P.; Chen, H.; Wang, J.; Ong, H.C.; Leung, K.C-F.; Ho, H.P.; Kong, S.K. In vitro effect of CTAB- and PEG-coated gold nanorods on the induction of eryptosis/erythroptosis in human erythrocytes. Nanotoxicology, 2012, 6(8), 847-856.
[http://dx.doi.org/10.3109/17435390.2011.625132] [PMID: 22022996]
[77]
Asharani, P.; Sethu, S.; Vadukumpully, S.; Zhong, S.; Lim, C.T.; Hande, M.P.; Valiyaveettil, S. Investigations on the structural damage in human erythrocytes exposed to silver, gold, and platinum nanoparticles. Adv. Funct. Mater., 2010, 20(8), 1233-1242.
[http://dx.doi.org/10.1002/adfm.200901846]
[78]
Laloy, J.; Minet, V.; Alpan, L.; Mullier, F.; Beken, S.; Toussaint, O.; Lucas, S.; Dogné, J-M. Impact of silver nanoparticles on haemolysis, platelet function and coagulation. Nanobiomedicine (Rij), 2014, 1, 4.
[http://dx.doi.org/10.5772/59346] [PMID: 30023015]
[79]
Ferdous, Z.; Beegam, S.; Tariq, S.; Ali, B.H.; Nemmar, A. The in vitro effect of polyvinylpyrrolidone and citrate coated silver nanoparticles on erythrocytic oxidative damage and eryptosis. Cell. Physiol. Biochem., 2018, 49(4), 1577-1588.
[http://dx.doi.org/10.1159/000493460] [PMID: 30223265]
[80]
Kwon, T.; Woo, H.J.; Kim, Y.H.; Lee, H.J.; Park, K.H.; Park, S.; Youn, B. Optimizing hemocompatibility of surfactant-coated silver nanoparticles in human erythrocytes. J. Nanosci. Nanotechnol., 2012, 12(8), 6168-6175.
[http://dx.doi.org/10.1166/jnn.2012.6433] [PMID: 22962723]
[81]
Bankapur, A.; Barkur, S.; Chidangil, S.; Mathur, D. A micro-Raman study of live, single red blood cells (RBCs) treated with AgNO3 nanoparticles. PLoS One, 2014, 9(7), e103493.
[http://dx.doi.org/10.1371/journal.pone.0103493] [PMID: 25057913]
[82]
Ashokraja, C.; Sakar, M.; Balakumar, S. A perspective on the hemolytic activity of chemical and green-synthesized silver and silver oxide nanoparticles. Mater. Res. Express, 2017, 4(10), 105406.
[http://dx.doi.org/10.1088/2053-1591/aa90f2]
[83]
Liu, T.; Han, S.; Pang, M.; Li, J.; Wang, J.; Luo, X.; Wang, Y.; Liu, Z.; Yang, X.; Ye, Z. Cerium oxide nanoparticles protect red blood cells from hyperthermia-induced damages. J. Biomater. Appl., 2021, 36(1), 36-44.
[http://dx.doi.org/10.1177/0885328220979091] [PMID: 33353468]
[84]
Tsamesidis, I.; Kazeli, K.; Lymperaki, E.; Pouroutzidou, G.K.; Oikonomou, I.M.; Komninou, P.; Zachariadis, G.; Reybier, K.; Pantaleo, A.; Kontonasaki, E. Effect of sintering temperature of bioactive glass nanoceramics on the hemolytic activity and oxidative stress biomarkers in erythrocytes. Cell. Mol. Bioeng., 2020, 13(3), 201-218.
[http://dx.doi.org/10.1007/s12195-020-00614-3] [PMID: 32426058]
[85]
Tsamesidis, I.; Kazeli, K.; Pouroutzidou, G.; Tsamesidis, I.; Pantaleo, A.; Lymperaki, E.; Kontonasaki, E. Evaluation of hemolytic activity and oxidative stress biomarkers in erythrocytes after exposure to bioactive glass nanoceramics; Beilstein Archives, 2019.
[http://dx.doi.org/10.3762/bxiv.2019.85.v1]
[86]
Belousov, A.; Belousova, E. Reducing of erythrocytes destruction by means of medicine nanotechnology(magnet-controlled sorbent (MCS-B). J. Cell. Mol. Biol., 2017, 2(1), 005.
[87]
Andrey, B.; Elena, M.; Vadim, Y.; Ekateryna, B. Stabilizing effect of magnetite nanoparticles (ICNB) on molecular structure of the proteins and lipids bonds of membranes of preserved RBCs. SOJ Anesthesiol. Pain Manag., 2019, 6(1), 1-10.
[88]
Rodrigues, R.O.; Bañobre-López, M.; Gallo, J.; Tavares, P.B.; Silva, A.M.; Lima, R.; Gomes, H.T. Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: A high-sensitivity microfluidic tool. J. Nanopart. Res., 2016, 18(7), 1-17.
[http://dx.doi.org/10.1007/s11051-016-3498-7]
[89]
Ran, Q.; Xiang, Y.; Liu, Y.; Xiang, L.; Li, F.; Deng, X.; Xiao, Y.; Chen, L.; Chen, L.; Li, Z. Eryptosis indices as a novel predictive parameter for biocompatibility of Fe3O4 magnetic nanoparticles on erythrocytes. Sci. Rep., 2015, 5(1), 1-15.
[http://dx.doi.org/10.1038/srep16209]
[90]
Aula, S.; Lakkireddy, S.; Swamy, A.; Kapley, A.; Jamil, K.; Tata, N.R.; Hembram, K. Biological interactions in vitro of zinc oxide nanoparticles of different characteristics. Mater. Res. Express, 2014, 1(3), 035041.
[http://dx.doi.org/10.1088/2053-1591/1/3/035041]
[91]
Jiang, Y.; Li, Y.; Richard, C.; Scherman, D.; Liu, Y. Hemocompatibility investigation and improvement of near-infrared persistent luminescent nanoparticle ZnGa2O4: Cr 3+ by surface PEGylation. J. Mater. Chem. B Mater. Biol. Med., 2019, 7(24), 3796-3803.
[http://dx.doi.org/10.1039/C9TB00378A]
[92]
Wani, M.R.; Shadab, G.H.A. Low doses of thymoquinone protect isolated human blood cells from TiO2 nanoparticles induced oxidative stress, hemolysis, cytotoxicity, DNA damage and collapse of mitochondrial activity. Phytomedicine Plus, 2021, 1(4), 100056.
[http://dx.doi.org/10.1016/j.phyplu.2021.100056]
[93]
Stella, A. Biological consequences from interaction of nanosized titanium (iv) oxides with defined human blood components. ProQuest Dissertations and Theses; Thesis (Ph.D.) University of Massachusetts Lowell, Lowell, MA, USA, 2014.
[94]
Imran, M.; Riaz, S.; Shah, S.M.H.; Batool, T.; Khan, H.N.; Sabri, A.N.; Naseem, S. In-vitro hemolytic activity and free radical scavenging by sol-gel synthesized Fe3O4 stabilized ZrO2 nanoparticles. Arab. J. Chem., 2020, 13(11), 7598-7608.
[http://dx.doi.org/10.1016/j.arabjc.2020.08.027]
[95]
Zhu, W.; Guo, J.; Agola, J.O.; Croissant, J.G.; Wang, Z.; Shang, J.; Coker, E.; Motevalli, B.; Zimpel, A.; Wuttke, S.; Brinker, C.J. Metal-organic framework nanoparticle-assisted cryopreservation of red blood cells. J. Am. Chem. Soc., 2019, 141(19), 7789-7796.
[http://dx.doi.org/10.1021/jacs.9b00992] [PMID: 31017405]
[96]
Vinardell, M.; Sordé, A.; Díaz, J.; Baccarin, T.; Mitjans, M. Comparative effects of macro-sized aluminum oxide and aluminum oxide nanoparticles on erythrocyte hemolysis: Influence of cell source, temperature, and size. J. Nanopart. Res., 2015, 17(2), 1-10.
[http://dx.doi.org/10.1007/s11051-015-2893-9]
[97]
Hecold, M.; Buczkowska, R.; Mucha, A.; Grzesiak, J.; Rac-Rumijowska, O.; Teterycz, H.; Marycz, K. The effect of PEI and PVP-stabilized gold nanoparticles on equine platelets activation: Potential application in equine regenerative medicine. J. Nanomater., 2017, 2017, 8706921.
[98]
Marycz, K.; Kolankowski, J.; Grzesiak, J.; Hecold, M.; Rac, O.; Teterycz, H. Application of gold nanoparticles of different concentrations to improve the therapeutic potential of autologous conditioned serum: Potential implications for equine regenerative medicine. J. Nanomater., 2015, 2015, 521207.
[http://dx.doi.org/10.1155/2015/521207]
[99]
Del Turco, S.; Ciofani, G.; Cappello, V.; Parlanti, P.; Gemmi, M.; Caselli, C.; Ragusa, R.; Papa, A.; Battaglia, D.; Sabatino, L.; Basta, G.; Mattoli, V. Effects of cerium oxide nanoparticles on hemostasis: Coagulation, platelets, and vascular endothelial cells. J. Biomed. Mater. Res. A, 2019, 107(7), 1551-1562.
[http://dx.doi.org/10.1002/jbm.a.36669] [PMID: 30882978]
[100]
Deb, S.; Raja, S.O.; Dasgupta, A.K.; Sarkar, R.; Chattopadhyay, A.P.; Chaudhuri, U.; Guha, P.; Sardar, P. Surface tunability of nanoparticles in modulating platelet functions. Blood Cells Mol. Dis., 2012, 48(1), 36-44.
[http://dx.doi.org/10.1016/j.bcmd.2011.09.011] [PMID: 22033068]
[101]
Mehrizi, T.Z. An overview of the latest applications of platelet-derived microparticles and nanoparticles in medical technology 2010-2020. Curr. Mol. Med., 2022, 22(6), 524-539.
[http://dx.doi.org/10.2174/1566524021666210928152015] [PMID: 34602037]
[102]
You, J.; Zhou, J.; Zhou, M.; Liu, Y.; Robertson, J.D.; Liang, D.; Van Pelt, C.; Li, C. Pharmacokinetics, clearance, and biosafety of polyethylene glycol-coated hollow gold nanospheres. Part. Fibre Toxicol., 2014, 11(1), 26.
[http://dx.doi.org/10.1186/1743-8977-11-26] [PMID: 24886070]
[103]
Deb, S.; Patra, H.K.; Lahiri, P.; Dasgupta, A.K.; Chakrabarti, K.; Chaudhuri, U. Multistability in platelets and their response to gold nanoparticles. Nanomedicine, 2011, 7(4), 376-384.
[http://dx.doi.org/10.1016/j.nano.2011.01.007] [PMID: 21310267]
[104]
Aseychev, A.V.; Azizova, O.A.; Beckman, E.M.; Dudnik, L.B.; Sergienko, V.I. Effect of gold nanoparticles coated with plasma components on ADP-induced platelet aggregation. Bull. Exp. Biol. Med., 2013, 155(5), 685-688.
[http://dx.doi.org/10.1007/s10517-013-2226-x] [PMID: 24288740]
[105]
Tian, Y.; Zhao, Y.; Zheng, W.; Zhang, W.; Jiang, X. Antithrombotic functions of small molecule-capped gold nanoparticles. Nanoscale, 2014, 6(15), 8543-8550.
[http://dx.doi.org/10.1039/C4NR01937G] [PMID: 24965704]
[106]
Santos-Martinez, M.J.; Rahme, K.; Corbalan, J.J.; Faulkner, C.; Holmes, J.D.; Tajber, L.; Medina, C.; Radomski, M.W. Pegylation increases platelet biocompatibility of gold nanoparticles. J. Biomed. Nanotechnol., 2014, 10(6), 1004-1015.
[http://dx.doi.org/10.1166/jbn.2014.1813] [PMID: 24749395]
[107]
Bandyopadhyay, D.; Baruah, H.; Gupta, B.; Sharma, S. Silver nano particles prevent platelet adhesion on immobilized fibrinogen. Indian J. Clin. Biochem., 2012, 27(2), 164-170.
[http://dx.doi.org/10.1007/s12291-011-0169-4] [PMID: 23543820]
[108]
Lateef, A.; Ojo, S.A.; Oladejo, S.M. Anti-candida, anti-coagulant and thrombolytic activities of biosynthesized silver nanoparticles using cell-free extract of Bacillus safensis LAU 13. Process Biochem., 2016, 51(10), 1406-1412.
[http://dx.doi.org/10.1016/j.procbio.2016.06.027]
[109]
Martínez-Gutierrez, F.; Thi, E.P.; Silverman, J.M.; de Oliveira, C.C.; Svensson, S.L.; Vanden Hoek, A.; Sánchez, E.M.; Reiner, N.E.; Gaynor, E.C.; Pryzdial, E.L.; Conway, E.M.; Orrantia, E.; Ruiz, F.; Av-Gay, Y.; Bach, H. Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanomedicine, 2012, 8(3), 328-336.
[http://dx.doi.org/10.1016/j.nano.2011.06.014] [PMID: 21718674]
[110]
Milić, M.; Vuković, B.; Barbir, R.; Pem, B.; Milić, M.; Šerić, V.; Frőhlich, E.; Vinković Vrček, I. Effect of differently coated silver nanoparticles on hemostasis. Platelets, 2021, 32(5), 651-661.
[http://dx.doi.org/10.1080/09537104.2020.1792432] [PMID: 32668997]
[111]
Hajtuch, J.; Hante, N.; Tomczyk, E.; Wojcik, M.; Radomski, M.W.; Santos-Martinez, M.J.; Inkielewicz-Stepniak, I. Effects of functionalized silver nanoparticles on aggregation of human blood platelets. Int. J. Nanomedicine, 2019, 14, 7399-7417.
[http://dx.doi.org/10.2147/IJN.S213499] [PMID: 31571858]
[112]
Asghar, M.A.; Yousuf, R.I.; Shoaib, M.H.; Asghar, M.A. Antibacterial, anticoagulant and cytotoxic evaluation of biocompatible nanocomposite of chitosan loaded green synthesized bioinspired silver nanoparticles. Int. J. Biol. Macromol., 2020, 160, 934-943.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.05.197] [PMID: 32470586]
[113]
Ragaseema, V.M.; Unnikrishnan, S.; Kalliyana Krishnan, V.; Krishnan, L.K. The antithrombotic and antimicrobial properties of PEG-protected silver nanoparticle coated surfaces. Biomaterials, 2012, 33(11), 3083-3092.
[http://dx.doi.org/10.1016/j.biomaterials.2012.01.005] [PMID: 22284585]
[114]
Makarchian, H.R.; Kasraianfard, A.; Ghaderzadeh, P.; Javadi, S.M.R.; Ghorbanpoor, M. The effectiveness of heparin, Platelet-Rich Plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats. Acta Cir. Bras., 2017, 32(1), 22-27.
[http://dx.doi.org/10.1590/s0102-865020170103] [PMID: 28225914]
[115]
Khorshidi, H.; Haddadi, P.; Raoofi, S.; Badiee, P.; Dehghani Nazhvani, A. Does adding silver nanoparticles to leukocyte-and platelet-rich fibrin improve its properties? Biomed Res. Int., 2018, 2018, 8515829.
[http://dx.doi.org/10.1155/2018/8515829]
[116]
Vinayagam, R.; Varadavenkatesan, T.; Selvaraj, R. Evaluation of the anticoagulant and catalytic activities of the Bridelia retusa fruit extract-functionalized silver nanoparticles. J. Cluster Sci., 2017, 28(5), 2919-2932.
[http://dx.doi.org/10.1007/s10876-017-1270-5]
[117]
Krishnaraj, R.N.; Berchmans, S. in vitro antiplatelet activity of silver nanoparticles synthesized using the microorganism Gluconobacter roseus: An AFM-based study. RSC Advances, 2013, 3(23), 8953-8959.
[http://dx.doi.org/10.1039/c3ra41246f]
[118]
Krystofiak, E.S. Fibrinogen-Conjugated Gold-coated Magnetite Nanoparticles for Antiplatelet Therapy. Theses and Dissertation. University of Wisconsin-Milwaukee, Milwaukee, USA, 2013.
[119]
Douglass, M.E.; Goudie, M.J.; Pant, J.; Singha, P.; Hopkins, S.; Devine, R.; Schmiedt, C.W.; Handa, H. Catalyzed nitric oxide release via Cu nanoparticles leads to an increase in antimicrobial effects and hemocompatibility for short-term extracorporeal circulation. ACS Appl. Bio Mater., 2019, 2(6), 2539-2548.
[http://dx.doi.org/10.1021/acsabm.9b00237] [PMID: 33718805]
[120]
Lingaraju, K.; Basavaraj, R.; Jayanna, K.; Bhavana, S.; Devaraja, S.; Swamy, H.K.; Nagaraju, G.; Nagabhushana, H.; Naika, H.R. Biocompatible fabrication of TiO2 nanoparticles: Antimicrobial, anticoagulant, antiplatelet, direct hemolytic and cytotoxicity properties. Inorg. Chem. Commun., 2021, 127, 108505.
[http://dx.doi.org/10.1016/j.inoche.2021.108505]
[121]
Nemmar, A.; Al-Salam, S.; Beegam, S.; Yuvaraju, P.; Ali, B.H. The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice. Int. J. Nanomedicine, 2017, 12, 2913-2922.
[http://dx.doi.org/10.2147/IJN.S127180] [PMID: 28435267]
[122]
Parlak, Z.V.; Wein, S.; Zybała, R.; Tymicki, E.; Kaszyca, K.; Rütten, S.; Labude, N.; Telle, R.; Schickle, K.; Neuss, S. High-strength ceramics as innovative candidates for cardiovascular implants. J. Biomater. Appl., 2019, 34(4), 585-596.
[http://dx.doi.org/10.1177/0885328219861602] [PMID: 31315481]
[123]
Laloy, J.; Haguet, H.; Alpan, L.; Raichman, D.; Dogné, J.M.; Lellouche, J.P. Impact of functional inorganic nanotubes f-INTs-WS on hemolysis, platelet function and coagulation. Nano Converg., 2018, 5, 31.
[124]
Guo, J.; Yu, Y.; Zhu, W.; Serda, R.E.; Franco, S.; Wang, L.; Lei, Q.; Agola, J.O.; Noureddine, A.; Ploetz, E.; Wuttke, S.; Brinker, C.J. Modular assembly of red blood cell superstructures from metal–organic framework nanoparticle‐based building blocks. Adv. Funct. Mater., 2021, 31(10), 2005935.
[http://dx.doi.org/10.1002/adfm.202005935]
[125]
Elsayed, H.H.; Al-Sherbini, A.S.A.; Abd-Elhady, E.E.; Ahmed, K.A.E.A. Treatment of anemia progression via magnetite and folate nanoparticles in vivo. Int. Sch. Res. Notices, 2014, 2014, 287575.
[http://dx.doi.org/10.1155/2014/287575]
[126]
Zhao, A.; Zhou, S.; Wang, Y.; Chen, J.; Ye, C.; Huang, N. Molecular interaction of fibrinogen with thermally modified titanium dioxide nanoparticles. RSC Adv., 2014, 4(76), 40428-40434.
[http://dx.doi.org/10.1039/C4RA07803A]

Rights & Permissions Print Cite
Article Metrics
32
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy