Back to Journals » International Journal of Nanomedicine » Volume 7

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

Authors Slastnikova, Rosenkranz, Gulak PV, Schiffelers, Lupanova, Khramtsov, Zalutsky, Sobolev A

Received 15 November 2011

Accepted for publication 6 December 2011

Published 2 February 2012 Volume 2012:7 Pages 467—482


Review by Single-blind

Peer reviewer comments 3

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 Sobolev1,2
1Laboratory 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, USA

Background: 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 α-melanocyte-stimulating hormone (αMSH) 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{αMSH}, 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{αMSH} yielded 89%–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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other articles by this author:

Development and evaluation of a new modular nanotransporter for drug delivery into nuclei of pathological cells expressing folate receptors

Slastnikova TA, Rosenkranz AA, Khramtsov YV, Karyagina TS, Ovechko SA, Sobolev AS

Drug Design, Development and Therapy 2017, 11:1315-1334

Published Date: 26 April 2017

Preparation, cytotoxicity, and in vivo antitumor efficacy of 111In-labeled modular nanotransporters

Slastnikova TA, Rosenkranz AA, Morozova NB, Vorontsova MS, Petriev VM, Lupanova TN, Ulasov AV, Zalutsky MR, Yakubovskaya RI, Sobolev AS

International Journal of Nanomedicine 2017, 12:395-410

Published Date: 10 January 2017

Readers of this article also read:

Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia

Hoggatt J, Tate TA, Pelus LM

International Journal of Nanomedicine 2015, 10:2647-2652

Published Date: 1 April 2015

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity

Leite EA, Souza CM, Carvalho-Júnior AD, Coelho LG, Lana AM, Cassali GD, Oliveira MC

International Journal of Nanomedicine 2012, 7:5259-5269

Published Date: 9 October 2012

Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson’s disease

Bossolasco P, Cova L, Levandis G, Diana V, Cerri S, Lambertenghi Deliliers G, Polli E, Silani V, Blandini F, Armentero MT

International Journal of Nanomedicine 2012, 7:435-447

Published Date: 31 January 2012

Lipid nanoparticles as delivery vehicles for the Parietaria judaica major allergen Par j 2

Bondì ML, Montana G, Craparo EF, Di Gesù R, Giammona G, Bonura A, Colombo P

International Journal of Nanomedicine 2011, 6:2953-2962

Published Date: 21 November 2011

Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs

Axiak SM, Selting KA, Decedue CJ, Henry CJ, Tate D, Howell J, Bilof KJ, Kim DY

International Journal of Nanomedicine 2011, 6:2205-2212

Published Date: 11 October 2011

Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin

Ahangari Cohan R, Madadkar-Sobhani A, Khanahmad H, Roohvand F, Aghasadeghi MR, Hedayati MH, Barghi Z, Shafiee Ardestani M, Nouri Inanlou D, Norouzian D

International Journal of Nanomedicine 2011, 6:1217-1227

Published Date: 15 June 2011

Aripiprazole in the treatment of Huntington’s disease: a case series

Andrea Ciammola, Jenny Sassone, Clarissa Colciago, Niccolò E Mencacci, Barbara Poletti, et al

Neuropsychiatric Disease and Treatment 2009, 5:1-4

Published Date: 25 November 2008

Direct and indirect effects of paliperidone extended-release tablets on negative symptoms of schizophrenia

Ibrahim Turkoz, Cynthia A Bossie, Bryan Dirks, Carla M Canuso

Neuropsychiatric Disease and Treatment 2008, 4:949-958

Published Date: 10 October 2008