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Volume 14, Issue 4
  • ISSN: 2210-3031
  • E-ISSN: 2210-304X

Abstract

Background

Plasma protein binding is inevitable for nanomaterials injected into blood circulation. For liposomes, this process is affected by the lipid composition of the bilayer. Membrane constituents and their ratio define liposome characteristics, namely, surface charge and hydrophobicity, which drive protein adsorption. Roughly 30 years ago, the correlation between the amount of bound proteins and the resulting circulation time of liposomes was established by S. Semple, A. Chonn, and P. Cullis. Here, we have estimated plasma protein binding, primarily to determine the impact of melphalan prodrug inclusion into bilayer on bare, PEGylated (stealth), and Sialyl Lewis X (SiaLeX)-decorated liposomes.

Experimental

Liposomes were allowed to bind plasma proteins for 15 minutes, then liposome-protein complexes were isolated, and protein and lipid quantities were assessed in the complexes. In addition, the uptake by activated HUVEC cells was evaluated for SiaLeX-decorated liposomes.

Results

Melphalan moieties on the bilayer surface enrich protein adsorption compared to pure phosphatidylcholine sample. Although PEG-lipid had facilitated a significant decrease in protein adsorption in the control sample, when prodrug was added to the composition, the degree of protein binding was restored to the level of melphalan liposomes without a stealth barrier. A similar effect was observed for SiaLeX-decorated liposomes.

Conclusion

None of the compositions reported here should suffer from quick elimination from circulation, according to the cut-off values introduced by Cullis and colleagues. Nevertheless, the amount of bound proteins is sufficient to affect biodistribution, namely, to impair receptor recognition of SiaLeX and reduce liposome uptake by endothelial cells.

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2024-11-26

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References

  1. BulbakeU. DoppalapudiS. KommineniN. KhanW. Liposomal formulations in clinical use: An updated review.Pharmaceutics2017941210.3390/pharmaceutics9020012 28346375
     [Google Scholar]
  2. LargeD.E. AbdelmessihR.G. FinkE.A. AugusteD.T. Liposome composition in drug delivery design, synthesis, characterization, and clinical application.Adv. Drug Deliv. Rev.202117611385110.1016/j.addr.2021.113851 34224787
     [Google Scholar]
  3. NsairatH. KhaterD. SayedU. OdehF. Al BawabA. AlshaerW. Liposomes: Structure, composition, types, and clinical applications.Heliyon202285e0939410.1016/j.heliyon.2022.e09394 35600452
     [Google Scholar]
  4. TseuG.Y.W. KamaruzamanK.A. A review of different types of liposomes and their advancements as a form of gene therapy treatment for breast cancer.Molecules2023283149810.3390/molecules28031498 36771161
     [Google Scholar]
  5. ZylberbergC. MatosevicS. Pharmaceutical liposomal drug delivery: A review of new delivery systems and a look at the regulatory landscape.Drug Deliv.20162393319332910.1080/10717544.2016.1177136 27145899
     [Google Scholar]
  6. FultonM.D. Najahi-MissaouiW. Liposomes in cancer therapy: How did we start and where are we now.Int. J. Mol. Sci.2023247661510.3390/ijms24076615 37047585
     [Google Scholar]
  7. OnishchenkoN. TretiakovaD. VodovozovaE. Spotlight on the protein corona of liposomes.Acta Biomater.2021134577810.1016/j.actbio.2021.07.074 34364016
     [Google Scholar]
  8. QuagliariniE. DigiacomoL. RenziS. PozziD. CaraccioloG. A decade of the liposome-protein corona: Lessons learned and future breakthroughs in theranostics.Nano Today20224710165710.1016/j.nantod.2022.101657
     [Google Scholar]
  9. SinghN. MaretsC. BoudonJ. MillotN. SaviotL. MauriziL. In vivo protein corona on nanoparticles: Does the control of all material parameters orient the biological behavior?Nanoscale Adv.2021351209122910.1039/D0NA00863J 36132858
     [Google Scholar]
  10. LasicD.D. MartinF.J. GabizonA. HuangS.K. PapahadjopoulosD. Sterically stabilized liposomes: A hypothesis on the molecular origin of the extended circulation times.Biochim. Biophys. Acta Biomembr.19911070118719210.1016/0005‑2736(91)90162‑2 1751525
     [Google Scholar]
  11. AllenT.M. HansenC. RutledgeJ. Liposomes with prolonged circulation times: Factors affecting uptake by reticuloendothelial and other tissues.Biochim. Biophys. Acta Biomembr.19899811273510.1016/0005‑2736(89)90078‑3 2719971
     [Google Scholar]
  12. StormG. BelliotS.O. DaemenT. LasicD.D. Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system.Adv. Drug Deliv. Rev.1995171314810.1016/0169‑409X(95)00039‑A
     [Google Scholar]
  13. LiuT. ChoiH. ZhouR. ChenI.W. RES blockade: A strategy for boosting efficiency of nanoparticle drug.Nano Today2015101112110.1016/j.nantod.2014.12.003
     [Google Scholar]
  14. ChonnA. SempleS.C. CullisP.R. Association of blood proteins with large unilamellar liposomes in vivo relation to circulation lifetimes.J. Biol. Chem.199226726187591876510.1016/S0021‑9258(19)37026‑7 1527006
     [Google Scholar]
  15. SempleS.C. ChonnA. CullisP.R. Interactions of liposomes and lipid-based carrier systems with blood proteins: Relation to clearance behaviour in vivo.Adv. Drug Deliv. Rev.1998321-231710.1016/S0169‑409X(97)00128‑2 10837632
     [Google Scholar]
  16. DiJ. GaoX. DuY. ZhangH. GaoJ. ZhengA. Size, shape, charge and “stealthy” surface: Carrier properties affect the drug circulation time in vivo.Asian J. Pharm. Sci.202116444445810.1016/j.ajps.2020.07.005 34703494
     [Google Scholar]
  17. IbrahimM. RamadanE. ElsadekN.E. EmamS.E. ShimizuT. AndoH. IshimaY. ElgarhyO.H. SarhanH.A. HusseinA.K. IshidaT. Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.J. Control. Release202235121523010.1016/j.jconrel.2022.09.031 36165835
     [Google Scholar]
  18. ZalbaS. ten HagenT.L.M. BurguiC. GarridoM.J. Stealth nanoparticles in oncology: Facing the PEG dilemma.J. Control. Release2022351223610.1016/j.jconrel.2022.09.002 36087801
     [Google Scholar]
  19. MünterR. StavnsbjergC. ChristensenE. ThomsenM.E. StensballeA. HansenA.E. ParhamifarL. KristensenK. SimonsenJ.B. LarsenJ.B. AndresenT.L. Unravelling heterogeneities in complement and antibody opsonization of individual liposomes as a function of surface architecture.Small20221814210652910.1002/smll.202106529 35187804
     [Google Scholar]
  20. SchöttlerS. BeckerG. WinzenS. SteinbachT. MohrK. LandfesterK. MailänderV. WurmF.R. Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers.Nat. Nanotechnol.201611437237710.1038/nnano.2015.330 26878141
     [Google Scholar]
  21. RampadoR. CrottiS. CalicetiP. PucciarelliS. AgostiniM. Recent advances in understanding the protein corona of nanoparticles and in the formulation of “stealthy” nanomaterials.Front. Bioeng. Biotechnol.2020816610.3389/fbioe.2020.00166 32309278
     [Google Scholar]
  22. XiaoQ. ZoulikhaM. QiuM. TengC. LinC. LiX. SallamM.A. XuQ. HeW. The effects of protein corona on in vivo fate of nanocarriers.Adv. Drug Deliv. Rev.202218611435610.1016/j.addr.2022.114356 35595022
     [Google Scholar]
  23. ZhangZ. GuanJ. JiangZ. YangY. LiuJ. HuaW. MaoY. LiC. LuW. QianJ. ZhanC. Brain-targeted drug delivery by manipulating protein corona functions.Nat. Commun.2019101356110.1038/s41467‑019‑11593‑z 31395892
     [Google Scholar]
  24. LiH. YinD. LiaoJ. WangY. GouR. TangC. LiW. LiuY. FuJ. ShiS. ZouL. Regulation of protein corona on liposomes using albumin-binding peptide for targeted tumor therapy.J. Control. Release202335559360310.1016/j.jconrel.2023.02.004 36773961
     [Google Scholar]
  25. FoxallC. WatsonS.R. DowbenkoD. FennieC. LaskyL.A. KisoM. HasegawaA. AsaD. BrandleyB.K. The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide.J. Cell Biol.1992117489590210.1083/jcb.117.4.895 1374413
     [Google Scholar]
  26. GaneshD. JainP. ShanthamurthyC.D. ToraskarS. KikkeriR. Targeting selectins mediated biological activities with multivalent probes.Front Chem.2021977302710.3389/fchem.2021.773027 34926401
     [Google Scholar]
  27. KuznetsovaN.R. StepanovaE.V. PeretolchinaN.M. KhochenkovD.A. BoldyrevI.A. BovinN.V. VodovozovaE.L. Targeting liposomes loaded with melphalan prodrug to tumour vasculature via the Sialyl Lewis X selectin ligand.J. Drug Target.201422324225010.3109/1061186X.2013.862805 24313904
     [Google Scholar]
  28. SempleS.C. ChonnA. Liposome-blood protein interactions in relation to liposome clearance.J. Liposome Res.199661336010.3109/08982109609037201
     [Google Scholar]
  29. Dos SantosN. AllenC. DoppenA.M. AnanthaM. CoxK.A.K. GallagherR.C. KarlssonG. EdwardsK. KennerG. SamuelsL. WebbM.S. BallyM.B. Influence of poly(ethylene glycol) grafting density and polymer length on liposomes: Relating plasma circulation lifetimes to protein binding.Biochim. Biophys. Acta Biomembr.2007176861367137710.1016/j.bbamem.2006.12.013 17400180
     [Google Scholar]
  30. TretiakovaD. SvirshchevskayaE. OnishchenkoN. AlekseevaA. BoldyrevI. KamyshinskyR. NatykanA. LokhmotovA. ArantsevaD. ShobolovD. VodovozovaE. Liposomal formulation of a melphalan lipophilic prodrug: Studies of acute toxicity, tolerability, and antitumor efficacy.Curr. Drug Deliv.202017431232310.2174/1567201817666200214105357 32056524
     [Google Scholar]
  31. TuzikovA.B. RyabukhinaE.V. ParamonovA.S. ChizhovA.O. BovinN.V. VodovozovaE.L. A convenient route to conjugates of 1,2-diglycerides with functionalized oligoethylene glycol spacer arms.Mendeleev Commun.202131453854110.1016/j.mencom.2021.07.034
     [Google Scholar]
  32. BoldyrevI.A. ZhaiX. MomsenM.M. BrockmanH.L. BrownR.E. MolotkovskyJ.G. New BODIPY lipid probes for fluorescence studies of membranes.J. Lipid Res.20074871518153210.1194/jlr.M600459‑JLR200 17416929
     [Google Scholar]
  33. OnishchenkoN.R. MoskovtsevA.A. KobanenkoM.K. TretiakovaD.S. AlekseevaA.S. KolesovD.V. MikryukovaA.A. BoldyrevI.A. KapkaevaM.R. ShcheglovitovaO.N. BovinN.V. KubatievA.A. TikhonovaO.V. VodovozovaE.L. Protein corona attenuates the targeting of antitumor sialyl lewis X-decorated liposomes to vascular endothelial cells under flow conditions.Pharmaceutics2023156175410.3390/pharmaceutics15061754 37376203
     [Google Scholar]
  34. TretiakovaD. KobanenkoM. AlekseevaA. BoldyrevI. KhaidukovS. ZgodaV. TikhonovaO. VodovozovaE. OnishchenkoN. Protein corona of anionic fluid-phase liposomes compromises their integrity rather than uptake by cells.Membranes202313768110.3390/membranes13070681 37505047
     [Google Scholar]
  35. MünterR. SimonsenJ.B. Comment on “Optimal centrifugal isolating of liposome-protein complexes from human plasma” by L. Digiacomo, F. Giulimondi, A. L. Capriotti, S. Piovesana, C. M. Montone, R. Z. Chiozzi, A. Laganá, M. Mahmoudi, D. Pozzi and G. Caracciolo, Nanoscale Adv., 2021, 3, 3824.Nanoscale Adv.20225129029910.1039/D2NA00343K 36605796
     [Google Scholar]
  36. MarkwellM.A.K. HaasS.M. BieberL.L. TolbertN.E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples.Anal. Biochem.197887120621010.1016/0003‑2697(78)90586‑9 98070
     [Google Scholar]
  37. TretiakovaD. KobanenkoM. Le-DeygenI. BoldyrevI. KudryashovaE. OnishchenkoN. VodovozovaE. Spectroscopy study of albumin interaction with negatively charged liposome membranes: Mutual structural effects of the protein and the bilayers.Membranes20221211103110.3390/membranes12111031 36363586
     [Google Scholar]
  38. JaffeE.A. NachmanR.L. BeckerC.G. MinickC.R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria.J. Clin. Invest.197352112745275610.1172/JCI107470 4355998
     [Google Scholar]
  39. ScheglovitovaO.N. RomanovY.A. MaksianinaE.V. SvintsitskayaV.A. ProninA.G. Herpes simplex type I virus infected human vascular endothelial cells induce the production of anti-viral and proinflammatory factors by peripheral blood leukocytes in vitro.Russ. J. Immunol.200272115122 12687253
     [Google Scholar]
  40. DelacreM. LeysC. MoraY.L. LakensD. Taking parametric assumptions seriously: Arguments for the use of Welch’s F-test instead of the classical F-test in one-way ANOVA.Rev. Int. Psychol. Soc.20193211310.5334/irsp.198
     [Google Scholar]
  41. Barba-BonA. NilamM. HennigA. Supramolecular chemistry in the biomembrane.ChemBioChem202021788691010.1002/cbic.201900646 31803982
     [Google Scholar]
  42. Le GrandoisJ. MarchioniE. ZhaoM. GiuffridaF. EnnaharS. BindlerF. Investigation of natural phosphatidylcholine sources: Separation and identification by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS2) of molecular species.J. Agric. Food Chem.200957146014602010.1021/jf900903e 19545117
     [Google Scholar]
  43. TretiakovaD. OnishchenkoN. BoldyrevI. MikhalyovI. TuzikovA. BovinN. EvtushenkoE. VodovozovaE. Influence of stabilizing components on the integrity of antitumor liposomes loaded with lipophilic prodrug in the bilayer.Colloids Surf. B Biointerfaces2018166455310.1016/j.colsurfb.2018.02.061 29533843
     [Google Scholar]
  44. SilviusJ.R. ZuckermannM.J. Interbilayer transfer of phospholipid-anchored macromolecules via monomer diffusion.Biochemistry199332123153316110.1021/bi00063a030 7681327
     [Google Scholar]
  45. BergerM. DegeyM. Leblond ChainJ. MaquoiE. EvrardB. LechanteurA. PielG. Effect of PEG anchor and serum on lipid nanoparticles: Development of a nanoparticles tracking method.Pharmaceutics202315259710.3390/pharmaceutics15020597 36839919
     [Google Scholar]
  46. KristensenK. UrquhartA.J. ThormannE. AndresenT.L. Binding of human serum albumin to PEGylated liposomes: Insights into binding numbers and dynamics by fluorescence correlation spectroscopy.Nanoscale2016847197261973610.1039/C6NR05455B 27874129
     [Google Scholar]
  47. TretiakovaD. Le-DeigenI. OnishchenkoN. KuntscheJ. KudryashovaE. VodovozovaE. Phosphatidylinositol Stabilizes Fluid-Phase Liposomes Loaded with a Melphalan Lipophilic Prodrug.Pharmaceutics202113447310.3390/pharmaceutics13040473 33915726
     [Google Scholar]
  48. SalvatiA. PitekA.S. MonopoliM.P. PrapainopK. BombelliF.B. HristovD.R. KellyP.M. ÅbergC. MahonE. DawsonK.A. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface.Nat. Nanotechnol.20138213714310.1038/nnano.2012.237 23334168
     [Google Scholar]
  49. FranciaV. YangK. DevilleS. Reker-SmitC. NelissenI. SalvatiA. Corona composition can affect the mechanisms cells use to internalize nanoparticles.ACS Nano20191310111071112110.1021/acsnano.9b03824 31525954
     [Google Scholar]
  50. YangK. Reker-SmitC. StuartM.C.A. SalvatiA. Effects of protein source on liposome uptake by cells: Corona composition and impact of the excess free proteins.Adv. Healthc. Mater.20211014210037010.1002/adhm.202100370 34050634
     [Google Scholar]
  51. MurrayK.S. RouseJ.C. TangaroneB.S. PetersonK.A. Van CleaveV.H. Identification of human serum interferants in the recombinant P-selectin glycoprotein ligand-1 clinical ELISA using MALDI MS and RP-HPLC.J. Immunol. Methods20012551-2415610.1016/S0022‑1759(01)00421‑5 11470285
     [Google Scholar]
  52. MarquesC. HajipourM.J. MaretsC. OudotA. Safavi-sohiR. GuilleminM. BorchardG. JordanO. SaviotL. MauriziL. Identification of the proteins determining the blood circulation time of nanoparticles.ACS Nano20231713124581247010.1021/acsnano.3c02041 37379064
     [Google Scholar]
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Plasma Protein Adsorption on Melphalan Prodrug Bearing Liposomes - Bare, Stealth, and Targeted
Drug Deliv Lett 14, 320 (2024); https://doi.org/10.2174/0122103031297263240612110749
/content/journals/ddl/10.2174/0122103031297263240612110749
/content/journals/ddl/10.2174/0122103031297263240612110749
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  • Article Type:     Letter
Keyword(s): lipophilic prodrug; liposome-protein complexes; Liposomes; melphalan; protein adsorption; protein binding value; Sialyl Lewis X
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