Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells

Mohamadreza Amin,1–3 Mahsa Bagheri,3 Mercedeh Mansourian,3 Mahmoud Reza Jaafari,3 Timo LM ten Hagen1 1Laboratory of Experimental Surgical Oncology, Section of Surgical Oncology, Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands; 2Cellular and Molecular Research Cen...

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Autores principales:	Amin M, Bagheri M, Mansourian M, Jaafari MR, ten Hagen TLM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	PEGylated liposomal doxorubicin TAT peptide ligand modified liposomes protein corona dysopsonization Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7f8b8454858a4123bebd91a98912004e
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spelling	oai:doaj.org-article:7f8b8454858a4123bebd91a98912004e2021-12-02T07:56:32ZRegulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells1178-2013https://doaj.org/article/7f8b8454858a4123bebd91a98912004e2018-11-01T00:00:00Zhttps://www.dovepress.com/regulation-of-in-vivo-behavior-of-tat-modified-liposome-by-associated--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mohamadreza Amin,1–3 Mahsa Bagheri,3 Mercedeh Mansourian,3 Mahmoud Reza Jaafari,3 Timo LM ten Hagen1 1Laboratory of Experimental Surgical Oncology, Section of Surgical Oncology, Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands; 2Cellular and Molecular Research Center, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran; 3Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran Introduction: PEGylated liposomes are widely used and studied as carriers for chemotherapeutics. While pharmacokinetics of the encapsulated drug is drastically altered resulting in favorable circulation time, improved tumor accumulation, and better manageable or reduced side effects, therapeutic efficacy has been disappointing. Major drawbacks are a failure to reach the tumor cell, limited penetration depth, and impaired uptake by tumor cells.Materials and methods: Here, we study the implication of HIV-1 transactivator of transcription (TAT)-derived peptides inserted on PEGylated liposomal doxorubicin (PLD) and followed in vitro and in vivo fate. PLDs were installed with 25–400 TAT peptides per liposome without an effect on PLD stability.Results: While TAT peptides facilitate active endocytosis of the carriers, we observed that these peptides did not promote endosomal escape or enhanced intracellular availability of doxorubicin. Interestingly, incorporation of TAT peptides did not change pharmacokinetics or biodistribution, which we found to result from a dysopsonization of the TAT-modified liposomes by serum proteins. A protein corona (PC) on TAT peptide-modified PLDs shields the active moieties and effectively reduces clearance of the TAT peptide containing nanoparticles. However, intratumoral activity was influenced by the number of TAT peptides present. The best antitumor efficacy was observed with a TAT peptide density of 100, while lower amounts showed results comparable to unmodified PLDs. At 200 TAT peptides, the preparation appeared to be least effective, which likely results from augmented interaction with tumor cells directly upon extravasation.Conclusion: We conclude that by optimizing TAT-modified PLDs, the occurring PC balances pharmacokinetics and tumor penetration through interference with avidity. Keywords: PEGylated liposomal doxorubicin, TAT peptide, ligand-modified liposomes, protein corona, dysopsonizationAmin MBagheri MMansourian MJaafari MRten Hagen TLMDove Medical PressarticlePEGylated liposomal doxorubicinTAT peptideligand modified liposomesprotein coronadysopsonizationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 7441-7455 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PEGylated liposomal doxorubicin TAT peptide ligand modified liposomes protein corona dysopsonization Medicine (General) R5-920
spellingShingle	PEGylated liposomal doxorubicin TAT peptide ligand modified liposomes protein corona dysopsonization Medicine (General) R5-920 Amin M Bagheri M Mansourian M Jaafari MR ten Hagen TLM Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells
description	Mohamadreza Amin,1–3 Mahsa Bagheri,3 Mercedeh Mansourian,3 Mahmoud Reza Jaafari,3 Timo LM ten Hagen1 1Laboratory of Experimental Surgical Oncology, Section of Surgical Oncology, Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands; 2Cellular and Molecular Research Center, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran; 3Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran Introduction: PEGylated liposomes are widely used and studied as carriers for chemotherapeutics. While pharmacokinetics of the encapsulated drug is drastically altered resulting in favorable circulation time, improved tumor accumulation, and better manageable or reduced side effects, therapeutic efficacy has been disappointing. Major drawbacks are a failure to reach the tumor cell, limited penetration depth, and impaired uptake by tumor cells.Materials and methods: Here, we study the implication of HIV-1 transactivator of transcription (TAT)-derived peptides inserted on PEGylated liposomal doxorubicin (PLD) and followed in vitro and in vivo fate. PLDs were installed with 25–400 TAT peptides per liposome without an effect on PLD stability.Results: While TAT peptides facilitate active endocytosis of the carriers, we observed that these peptides did not promote endosomal escape or enhanced intracellular availability of doxorubicin. Interestingly, incorporation of TAT peptides did not change pharmacokinetics or biodistribution, which we found to result from a dysopsonization of the TAT-modified liposomes by serum proteins. A protein corona (PC) on TAT peptide-modified PLDs shields the active moieties and effectively reduces clearance of the TAT peptide containing nanoparticles. However, intratumoral activity was influenced by the number of TAT peptides present. The best antitumor efficacy was observed with a TAT peptide density of 100, while lower amounts showed results comparable to unmodified PLDs. At 200 TAT peptides, the preparation appeared to be least effective, which likely results from augmented interaction with tumor cells directly upon extravasation.Conclusion: We conclude that by optimizing TAT-modified PLDs, the occurring PC balances pharmacokinetics and tumor penetration through interference with avidity. Keywords: PEGylated liposomal doxorubicin, TAT peptide, ligand-modified liposomes, protein corona, dysopsonization
format	article
author	Amin M Bagheri M Mansourian M Jaafari MR ten Hagen TLM
author_facet	Amin M Bagheri M Mansourian M Jaafari MR ten Hagen TLM
author_sort	Amin M
title	Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells
title_short	Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells
title_full	Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells
title_fullStr	Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells
title_full_unstemmed	Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells
title_sort	regulation of in vivo behavior of tat-modified liposome by associated protein corona and avidity to tumor cells
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/7f8b8454858a4123bebd91a98912004e
work_keys_str_mv	AT aminm regulationofinvivobehavioroftatmodifiedliposomebyassociatedproteincoronaandaviditytotumorcells AT bagherim regulationofinvivobehavioroftatmodifiedliposomebyassociatedproteincoronaandaviditytotumorcells AT mansourianm regulationofinvivobehavioroftatmodifiedliposomebyassociatedproteincoronaandaviditytotumorcells AT jaafarimr regulationofinvivobehavioroftatmodifiedliposomebyassociatedproteincoronaandaviditytotumorcells AT tenhagentlm regulationofinvivobehavioroftatmodifiedliposomebyassociatedproteincoronaandaviditytotumorcells
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Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells

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