Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery

Tatiana A Slastnikova1,2, Andrey A Rosenkranz1,2, Pavel V Gulak1, Raymond M Schiffelers3, Tatiana N Lupanova1,4, Yuri V Khramtsov1, Michael R Zalutsky5, Alexander S Sobolev1,21Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Moscow, Russia; 2Department of Bioph...

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Autores principales:	Slastnikova TA, Rosenkranz AA, Gulak PV, Schiffelers RM, Lupanova TN, Khramtsov YV, Zalutsky MR, Sobolev AS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/981d98348d6d4b7085f50fc12ef4a100
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spelling	oai:doaj.org-article:981d98348d6d4b7085f50fc12ef4a1002021-12-02T01:42:38ZModular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery1176-91141178-2013https://doaj.org/article/981d98348d6d4b7085f50fc12ef4a1002012-02-01T00:00:00Zhttp://www.dovepress.com/modular-nanotransporters-a-multipurpose-in-vivo-working-platform-for-t-a9198https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Tatiana A Slastnikova1,2, Andrey A Rosenkranz1,2, Pavel V Gulak1, Raymond M Schiffelers3, Tatiana N Lupanova1,4, Yuri V Khramtsov1, Michael R Zalutsky5, Alexander S Sobolev1,21Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Moscow, Russia; 2Department of Biophysics, Biological Faculty, Moscow State University, Vorobyevy Gory, Moscow, Russia; 3Laboratory for Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands; 4Department of Bioengineering, Biological Faculty, Moscow State University, Vorobyevy Gory, Moscow, Russia; 5Department of Radiology, Duke University Medical Center, Durham, NC, USABackground: Modular nanotransporters (MNT) are recombinant multifunctional polypeptides created to exploit a cascade of cellular processes, initiated with membrane receptor recognition to deliver selective short-range and highly cytotoxic therapeutics to the cell nucleus. This research was designed for in vivo concept testing for this drug delivery platform using two modular nanotransporters, one targeted to the &alpha;-melanocyte-stimulating hormone (&alpha;MSH) receptor overexpressed on melanoma cells and the other to the epidermal growth factor (EGF) receptor overexpressed on several cancers, including glioblastoma, and head-and-neck and breast carcinoma cells.Methods: In vivo targeting of the modular nanotransporter was determined by immunofluorescence confocal laser scanning microscopy and by accumulation of 125I-labeled modular nanotransporters. The in vivo therapeutic effects of the modular nanotransporters were assessed by photodynamic therapy studies, given that the cytotoxicity of photosensitizers is critically dependent on their delivery to the cell nucleus.Results: Immunohistochemical analyses of tumor and neighboring normal tissues of mice injected with multifunctional nanotransporters demonstrated preferential uptake in tumor tissue, particularly in cell nuclei. With 125I-labeled MNT{&alpha;MSH}, optimal tumor:muscle and tumor:skin ratios of 8:1 and 9.8:1, respectively, were observed 3 hours after injection in B16-F1 melanoma-bearing mice. Treatment with bacteriochlorin p-MNT{&alpha;MSH} yielded 89%&ndash;98% tumor growth inhibition and a two-fold increase in survival for mice with B16-F1 and Cloudman S91 melanomas. Likewise, treatment of A431 human epidermoid carcinoma-bearing mice with chlorin e6- MNT{EGF} resulted in 94% tumor growth inhibition compared with free chlorin e6, with 75% of animals surviving at 3 months compared with 0% and 20% for untreated and free chlorin e6-treated groups, respectively.Conclusion: The multifunctional nanotransporter approach provides a new in vivo functional platform for drug development that could, in principle, be applicable to any combination of cell surface receptor and agent (photosensitizers, oligonucleotides, radionuclides) requiring nuclear delivery to achieve maximum effectiveness.Keywords: drug delivery, nanobiotechnology, nanomedicine, cancer therapy, photosensitizers, multifunctional nanotransporterSlastnikova TARosenkranz AAGulak PVSchiffelers RMLupanova TNKhramtsov YVZalutsky MRSobolev ASDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 467-482 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Slastnikova TA Rosenkranz AA Gulak PV Schiffelers RM Lupanova TN Khramtsov YV Zalutsky MR Sobolev AS Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery
description	Tatiana A Slastnikova1,2, Andrey A Rosenkranz1,2, Pavel V Gulak1, Raymond M Schiffelers3, Tatiana N Lupanova1,4, Yuri V Khramtsov1, Michael R Zalutsky5, Alexander S Sobolev1,21Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Moscow, Russia; 2Department of Biophysics, Biological Faculty, Moscow State University, Vorobyevy Gory, Moscow, Russia; 3Laboratory for Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands; 4Department of Bioengineering, Biological Faculty, Moscow State University, Vorobyevy Gory, Moscow, Russia; 5Department of Radiology, Duke University Medical Center, Durham, NC, USABackground: Modular nanotransporters (MNT) are recombinant multifunctional polypeptides created to exploit a cascade of cellular processes, initiated with membrane receptor recognition to deliver selective short-range and highly cytotoxic therapeutics to the cell nucleus. This research was designed for in vivo concept testing for this drug delivery platform using two modular nanotransporters, one targeted to the &alpha;-melanocyte-stimulating hormone (&alpha;MSH) receptor overexpressed on melanoma cells and the other to the epidermal growth factor (EGF) receptor overexpressed on several cancers, including glioblastoma, and head-and-neck and breast carcinoma cells.Methods: In vivo targeting of the modular nanotransporter was determined by immunofluorescence confocal laser scanning microscopy and by accumulation of 125I-labeled modular nanotransporters. The in vivo therapeutic effects of the modular nanotransporters were assessed by photodynamic therapy studies, given that the cytotoxicity of photosensitizers is critically dependent on their delivery to the cell nucleus.Results: Immunohistochemical analyses of tumor and neighboring normal tissues of mice injected with multifunctional nanotransporters demonstrated preferential uptake in tumor tissue, particularly in cell nuclei. With 125I-labeled MNT{&alpha;MSH}, optimal tumor:muscle and tumor:skin ratios of 8:1 and 9.8:1, respectively, were observed 3 hours after injection in B16-F1 melanoma-bearing mice. Treatment with bacteriochlorin p-MNT{&alpha;MSH} yielded 89%&ndash;98% tumor growth inhibition and a two-fold increase in survival for mice with B16-F1 and Cloudman S91 melanomas. Likewise, treatment of A431 human epidermoid carcinoma-bearing mice with chlorin e6- MNT{EGF} resulted in 94% tumor growth inhibition compared with free chlorin e6, with 75% of animals surviving at 3 months compared with 0% and 20% for untreated and free chlorin e6-treated groups, respectively.Conclusion: The multifunctional nanotransporter approach provides a new in vivo functional platform for drug development that could, in principle, be applicable to any combination of cell surface receptor and agent (photosensitizers, oligonucleotides, radionuclides) requiring nuclear delivery to achieve maximum effectiveness.Keywords: drug delivery, nanobiotechnology, nanomedicine, cancer therapy, photosensitizers, multifunctional nanotransporter
format	article
author	Slastnikova TA Rosenkranz AA Gulak PV Schiffelers RM Lupanova TN Khramtsov YV Zalutsky MR Sobolev AS
author_facet	Slastnikova TA Rosenkranz AA Gulak PV Schiffelers RM Lupanova TN Khramtsov YV Zalutsky MR Sobolev AS
author_sort	Slastnikova TA
title	Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery
title_short	Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery
title_full	Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery
title_fullStr	Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery
title_full_unstemmed	Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery
title_sort	modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/981d98348d6d4b7085f50fc12ef4a100
work_keys_str_mv	AT slastnikovata modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery AT rosenkranzaa modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery AT gulakpv modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery AT schiffelersrm modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery AT lupanovatn modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery AT khramtsovyv modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery AT zalutskymr modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery AT sobolevas modularnanotransportersamultipurposeinvivoworkingplatformfortargeteddrugdelivery
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Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery

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