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Advanced Healthcare MaterialsVolume 6, Issue 21, 8 November 2017, Article number 1700597

Atomic Force Microscopy as a Tool to Assess the Specificity of Targeted Nanoparticles in Biological Models of High Complexity(Article)

  • aINEB – Instituto de Engenharia Biomédica, i3S – Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen 208, Porto, 4200-135, Portugal
  • bFaculdade de Engenharia da Universidade do Porto, R. Dr. Roberto Frias, Porto, 4200-465, Portugal
  • cFaculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, Porto, 4200-319, Portugal
  • dInstitute of Biophysics, Johannes Kepler University, Gruberstraße 40, Linz, 4020, Austria
  • eICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, Porto, 4050-313, Portugal

Abstract

The ability to design nanoparticle delivery systems capable of selectively target their payloads to specific cell populations is still a major caveat in nanomedicine. One of the main hurdles is the fact that each nanoparticle formulation needs to be precisely tuned to match the specificities of the target cell and route of administration. In this work, molecular recognition force spectroscopy (MRFS) is presented as a tool to evaluate the specificity of neuron-targeted trimethyl chitosan nanoparticles to neuronal cell populations in biological samples of different complexity. The use of atomic force microscopy tips functionalized with targeted or non-targeted nanoparticles made it possible to assess the specific interaction of each formulation with determined cell surface receptors in a precise fashion. More importantly, the combination of MRFS with fluorescent microscopy allowed to probe the nanoparticles vectoring capacity in models of high complexity, such as primary mixed cultures, as well as specific subcellular regions in histological tissues. Overall, this work contributes for the establishment of MRFS as a powerful alternative technique to animal testing in vector design and opens new avenues for the development of advanced targeted nanomedicines. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Author keywords

atomic force spectroscopyhistological tissue samplesnanoparticle designprimary co-culturestargeted nanomedicines

Indexed keywords

EMTREE drug terms:cell surface receptorchitosan nanoparticletrimethyl chitosan nanoparticleunclassified drug1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinoliniumbenzoxazole derivativechitosanpolymerquantum dotquinoline derivativetubulin
EMTREE medical terms:adultanimal cellanimal tissueArticleatomic force microscopybrain histologycell populationcontrolled studyembryomolecular recognition force spectroscopymousenerve cellnerve cell culturenonhumanpriority journalratanimalatomic force microscopybiological modelcell culturechemistrycytologyfluorescence microscopymetabolismnanomedicineNIH 3T3 cell lineplasmidproceduresspinal gangliontransmission electron microscopy
MeSH:AnimalsBenzoxazolesCells, CulturedChitosanGanglia, SpinalMiceMicroscopy, Atomic ForceMicroscopy, Electron, TransmissionMicroscopy, FluorescenceModels, BiologicalNanomedicineNIH 3T3 CellsPlasmidsPolymersQuantum DotsQuinolinium CompoundsTubulin

Chemicals and CAS Registry Numbers:

chitosan, 9012-76-4;

1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium; Benzoxazoles; Chitosan; Polymers; Quinolinium Compounds; Tubulin

Funding details

Funding sponsor Funding number Acronym
PTDC/CTM-NAN/115124/2009,SFRH/BD/79930/2011,SFRH/BD/77933/2011,UID/BIM/04293/2013,PTDC/CTM-NAN/3547/2014
Fundação para a Ciência e a Tecnologia
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  • 1

    The authors would like to acknowledge the Bioimaging Center for Biomaterials and Regenerative Therapies of INEB (b.IMAGE) for the support with atomic force and confocal microscopy, Centro de Materiais da Universidade do Porto (CEMUP) for NMR analysis and the Biointerfaces and Nanotechnology Service (INEB-i3S) for nanoparticle size and zeta-potential analysis. The work was financed by Portuguese funds through FCT (Funda??o para a Ci?ncia e a Tecnologia) in the framework of the projects UID/BIM/04293/2013, PTDC/CTM-NAN/115124/2009, and PTDC/CTM-NAN/3547/2014. C.P.G. and C.D.F.L. acknowledge FCT for their Ph.D. scholarships SFRH/BD/79930/2011 and SFRH/BD/77933/2011, respectively.

  • ISSN: 21922640
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1002/adhm.201700597
  • PubMed ID: 28752592
  • Document Type: Article
  • Publisher: Wiley-VCH Verlag

  Pêgo, A.P.; INEB – Instituto de Engenharia Biomédica, i3S – Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen 208, Porto, Portugal;
© Copyright 2017 Elsevier B.V., All rights reserved.

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