A smart viral vector for targeted delivery of hydrophobic drugs

Abstract Targeted delivery of hydrophobic chemotherapeutic drugs to tumor cells remains a fundamental problem in cancer therapy. Effective encapsulation of hydrophobic drugs in nano-vehicles can improve their pharmacokinetics, bioavailability and prevent off-target localization. We have devised a me...

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Autores principales:	Sukanya Ghosh, Manidipa Banerjee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4d01c6e351d44f7850f0f7d62f0455e
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spelling	oai:doaj.org-article:c4d01c6e351d44f7850f0f7d62f0455e2021-12-02T14:23:32ZA smart viral vector for targeted delivery of hydrophobic drugs10.1038/s41598-021-86198-y2045-2322https://doaj.org/article/c4d01c6e351d44f7850f0f7d62f0455e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86198-yhttps://doaj.org/toc/2045-2322Abstract Targeted delivery of hydrophobic chemotherapeutic drugs to tumor cells remains a fundamental problem in cancer therapy. Effective encapsulation of hydrophobic drugs in nano-vehicles can improve their pharmacokinetics, bioavailability and prevent off-target localization. We have devised a method for easy chemical conjugation and multivalent display of a tumor-homing peptide to virus-like particles of a non-mammalian virus, Flock House Virus (FHV), to engineer it into a smart vehicle for targeted delivery of hydrophobic drugs. This conjugation method provides dual functionalization to the VLPs, first, a 2 kDa PEG spacer arm shields VLPs from immune reactivity, and second, attachment of the tumor homing peptide tLyP-1 chauffeurs the encapsulated hydrophobic drugs to target cells. The fortuitous affinity of the FHV capsid towards hydrophobic molecules, and dependence on Ca2+ for maintaining a stable capsid shell, were utilized for incorporation of hydrophobic drugs—doxorubicin and ellipticine—in tLyP-1 conjugated VLPs. The drug release profile from the VLP was observed to be gradual, and strictly endosomal pH dependent. We propose that this accessible platform empowers surface functionalization of VLP with numerous ligands containing terminal cysteines, for generating competent delivery vehicles, antigenic display and other biomedical applications.Sukanya GhoshManidipa BanerjeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sukanya Ghosh Manidipa Banerjee A smart viral vector for targeted delivery of hydrophobic drugs
description	Abstract Targeted delivery of hydrophobic chemotherapeutic drugs to tumor cells remains a fundamental problem in cancer therapy. Effective encapsulation of hydrophobic drugs in nano-vehicles can improve their pharmacokinetics, bioavailability and prevent off-target localization. We have devised a method for easy chemical conjugation and multivalent display of a tumor-homing peptide to virus-like particles of a non-mammalian virus, Flock House Virus (FHV), to engineer it into a smart vehicle for targeted delivery of hydrophobic drugs. This conjugation method provides dual functionalization to the VLPs, first, a 2 kDa PEG spacer arm shields VLPs from immune reactivity, and second, attachment of the tumor homing peptide tLyP-1 chauffeurs the encapsulated hydrophobic drugs to target cells. The fortuitous affinity of the FHV capsid towards hydrophobic molecules, and dependence on Ca2+ for maintaining a stable capsid shell, were utilized for incorporation of hydrophobic drugs—doxorubicin and ellipticine—in tLyP-1 conjugated VLPs. The drug release profile from the VLP was observed to be gradual, and strictly endosomal pH dependent. We propose that this accessible platform empowers surface functionalization of VLP with numerous ligands containing terminal cysteines, for generating competent delivery vehicles, antigenic display and other biomedical applications.
format	article
author	Sukanya Ghosh Manidipa Banerjee
author_facet	Sukanya Ghosh Manidipa Banerjee
author_sort	Sukanya Ghosh
title	A smart viral vector for targeted delivery of hydrophobic drugs
title_short	A smart viral vector for targeted delivery of hydrophobic drugs
title_full	A smart viral vector for targeted delivery of hydrophobic drugs
title_fullStr	A smart viral vector for targeted delivery of hydrophobic drugs
title_full_unstemmed	A smart viral vector for targeted delivery of hydrophobic drugs
title_sort	smart viral vector for targeted delivery of hydrophobic drugs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c4d01c6e351d44f7850f0f7d62f0455e
work_keys_str_mv	AT sukanyaghosh asmartviralvectorfortargeteddeliveryofhydrophobicdrugs AT manidipabanerjee asmartviralvectorfortargeteddeliveryofhydrophobicdrugs AT sukanyaghosh smartviralvectorfortargeteddeliveryofhydrophobicdrugs AT manidipabanerjee smartviralvectorfortargeteddeliveryofhydrophobicdrugs
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A smart viral vector for targeted delivery of hydrophobic drugs

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