Flexible Nanoparticles Reach Sterically Obscured Endothelial Targets Inaccessible to Rigid Nanoparticles

Jacob W. Myerson, Bruce Braender, Olivia Mcpherson, Patrick M. Glassman, Raisa Y. Kiseleva, Vladimir V. Shuvaev, Oscar Marcos-Contreras, Martha E. Grady, Hyun Su Lee, Colin F. Greineder, Radu V. Stan, Russell J. Composto, David M. Eckmann, Vladimir R. Muzykantov

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Molecular targeting of nanoparticle drug carriers promises maximized therapeutic impact to sites of disease or injury with minimized systemic effects. Precise targeting demands addressing to subcellular features. Caveolae, invaginations in cell membranes implicated in transcytosis and inflammatory signaling, are appealing subcellular targets. Caveolar geometry has been reported to impose a ≈50 nm size cutoff on nanocarrier access to plasmalemma vesicle associated protein (PLVAP), a marker found in caveolae in the lungs. The use of deformable nanocarriers to overcome that size cutoff is explored in this study. Lysozyme-dextran nanogels (NGs) are synthesized with ≈150 or ≈300 nm mean diameter. Atomic force microscopy indicates the NGs deform on complementary surfaces. Quartz crystal microbalance data indicate that NGs form softer monolayers (≈60 kPa) than polystyrene particles (≈8 MPa). NGs deform during flow through microfluidic channels, and modeling of NG extrusion through porous filters yields sieving diameters less than 25 nm for NGs with 150 and 300 nm hydrodynamic diameters. NGs of 150 and 300 nm diameter target PLVAP in mouse lungs while counterpart rigid polystyrene particles do not. The data in this study indicate a role for mechanical deformability in targeting large high-payload drug-delivery vehicles to sterically obscured targets like PLVAP.

Original languageEnglish
Article number1802373
JournalAdvanced Materials
Issue number32
StatePublished - Aug 9 2018

Bibliographical note

Funding Information:
J.W.M. was supported by National Institutes of Health (NIH) T32 HL07915. P.M.G. was supported by NIH T32 HL007954. This study was supported in part by NIH grants RO1HL125462 (V.R.M.) and RO1EB006818 (D.M.E.) and by National Science Foundation (NSF)/Chemical, Bioengineering, Environmental and Transport Systems (CBET) 1706014 (R.J.C.). J.W.M., B.B., O.M., P.M.G., V.V.S., O.M.-C., M.E.G, R.Y.K., and C.F.G. performed the experiments. J.W.M., B.B., O.M., P.M.G., V.V.S., R.Y.K., D.M.E., and V.R.M. designed the experiments. J.W.M., P.M.G., M.E.G., H.-S.L., R.V.S., R.J.C., D.M.E., and V.R.M. analyzed results. J.W.M. and V.R.M. wrote the paper. The paper was reviewed by all authors and all authors approved of the submitted version.

Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


  • cell biology
  • functional nanoparticles
  • nanogels
  • nanomechanics
  • nanomedicine

ASJC Scopus subject areas

  • Materials Science (all)
  • Mechanics of Materials
  • Mechanical Engineering


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