Peptide GH625 Enters into Neuron and Astrocyte Cell Lines and Crosses the Blood-brain Barrier in Rats

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2015 Mar 21

PMID 25792823

Citations 26

Authors

Salvatore Valiante

Annarita Falanga

Luisa Cigliano

Giuseppina Iachetta

Rosa Anna Busiello

Valeria La Marca

Massimiliano Galdiero

Assunta Lombardi

Stefania Galdiero

Affiliations

Soon will be listed here.

Abstract

Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood-brain barrier (BBB). In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human diseases.

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References

Alyautdin R, Khalin I, Nafeeza M, Haron M, Kuznetsov D . Nanoscale drug delivery systems and the blood-brain barrier. Int J Nanomedicine. 2014; 9:795-811. PMC: 3926460. DOI: 10.2147/IJN.S52236. View

Dinda S, Pattnaik G . Nanobiotechnology-based drug delivery in brain targeting. Curr Pharm Biotechnol. 2014; 14(15):1264-74. DOI: 10.2174/1389201015666140608143719. View

Falanga A, Vitiello M, Cantisani M, Tarallo R, Guarnieri D, Mignogna E . A peptide derived from herpes simplex virus type 1 glycoprotein H: membrane translocation and applications to the delivery of quantum dots. Nanomedicine. 2011; 7(6):925-34. DOI: 10.1016/j.nano.2011.04.009. View

Bernacki J, Dobrowolska A, Nierwinska K, Malecki A . Physiology and pharmacological role of the blood-brain barrier. Pharmacol Rep. 2008; 60(5):600-22. View

Galdiero S, Vitiello M, Falanga A, Cantisani M, Incoronato N, Galdiero M . Intracellular delivery: exploiting viral membranotropic peptides. Curr Drug Metab. 2012; 13(1):93-104. DOI: 10.2174/138920012798356961. View

Pardridge W . Blood-brain barrier delivery. Drug Discov Today. 2007; 12(1-2):54-61. DOI: 10.1016/j.drudis.2006.10.013. View

Lanni A, Moreno M, Lombardi A, Goglia F . Calorigenic effect of diiodothyronines in the rat. J Physiol. 1996; 494 ( Pt 3):831-7. PMC: 1160681. DOI: 10.1113/jphysiol.1996.sp021536. View

Bertrand N, Leroux J . The journey of a drug-carrier in the body: an anatomo-physiological perspective. J Control Release. 2011; 161(2):152-63. DOI: 10.1016/j.jconrel.2011.09.098. View

Jones A . Gateways and tools for drug delivery: endocytic pathways and the cellular dynamics of cell penetrating peptides. Int J Pharm. 2007; 354(1-2):34-8. DOI: 10.1016/j.ijpharm.2007.10.046. View

10.

Demeule M, Regina A, Annabi B, Bertrand Y, Bojanowski M, Beliveau R . Brain endothelial cells as pharmacological targets in brain tumors. Mol Neurobiol. 2004; 30(2):157-83. DOI: 10.1385/MN:30:2:157. View

11.

Baschong W, Suetterlin R, Laeng R . Control of autofluorescence of archival formaldehyde-fixed, paraffin-embedded tissue in confocal laser scanning microscopy (CLSM). J Histochem Cytochem. 2001; 49(12):1565-72. DOI: 10.1177/002215540104901210. View

12.

Moros M, Mitchell S, Grazu V, de la Fuente J . The fate of nanocarriers as nanomedicines in vivo: important considerations and biological barriers to overcome. Curr Med Chem. 2013; 20(22):2759-78. DOI: 10.2174/0929867311320220003. View

13.

Dominguez A, Suarez-Merino B, Goni-de-Cerio F . Nanoparticles and blood-brain barrier: the key to central nervous system diseases. J Nanosci Nanotechnol. 2014; 14(1):766-79. DOI: 10.1166/jnn.2014.9119. View

14.

Fawell S, Seery J, Daikh Y, Moore C, Chen L, Pepinsky B . Tat-mediated delivery of heterologous proteins into cells. Proc Natl Acad Sci U S A. 1994; 91(2):664-8. PMC: 43009. DOI: 10.1073/pnas.91.2.664. View

15.

Rapaport D, Shai Y . Interaction of fluorescently labeled pardaxin and its analogues with lipid bilayers. J Biol Chem. 1991; 266(35):23769-75. View

16.

Borlongan C, Emerich D . Facilitation of drug entry into the CNS via transient permeation of blood brain barrier: laboratory and preliminary clinical evidence from bradykinin receptor agonist, Cereport. Brain Res Bull. 2003; 60(3):297-306. DOI: 10.1016/s0361-9230(03)00043-1. View

17.

Gabathuler R . Development of new peptide vectors for the transport of therapeutic across the blood-brain barrier. Ther Deliv. 2012; 1(4):571-86. DOI: 10.4155/tde.10.35. View

18.

Viegas M, Martins T, Seco F, do Carmo A . An improved and cost-effective methodology for the reduction of autofluorescence in direct immunofluorescence studies on formalin-fixed paraffin-embedded tissues. Eur J Histochem. 2007; 51(1):59-66. View

19.

Carberry T, Tarallo R, Falanga A, Finamore E, Galdiero M, Weck M . Dendrimer functionalization with a membrane-interacting domain of herpes simplex virus type 1: towards intracellular delivery. Chemistry. 2012; 18(43):13678-85. DOI: 10.1002/chem.201202358. View

20.

Guarnieri D, Falanga A, Muscetti O, Tarallo R, Fusco S, Galdiero M . Shuttle-mediated nanoparticle delivery to the blood-brain barrier. Small. 2012; 9(6):853-62. DOI: 10.1002/smll.201201870. View