Pair correlation microscopy reveals the role of nanoparticle shape in intracellular transport and site of drug release

Elizabeth Hinde, Kitiphume Thammasiraphop, Hien T.T. Duong, Jonathan Yeow, Bunyamin Karagoz, Cyrille Boyer, J. Justin Gooding, Katharina Gaus*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

291 Citations (Scopus)

Abstract

Nanoparticle size, surface charge and material composition are known to affect the uptake of nanoparticles by cells. However, whether nanoparticle shape affects transport across various barriers inside the cell remains unclear. Here we used pair correlation microscopy to show that polymeric nanoparticles with different shapes but identical surface chemistries moved across the various cellular barriers at different rates, ultimately defining the site of drug release. We measured how micelles, vesicles, rods and worms entered the cell and whether they escaped from the endosomal system and had access to the nucleus via the nuclear pore complex. Rods and worms, but not micelles and vesicles, entered the nucleus by passive diffusion. Improving nuclear access, for example with a nuclear localization signal, resulted in more doxorubicin release inside the nucleus and correlated with greater cytotoxicity. Our results therefore demonstrate that drug delivery across the major cellular barrier, the nuclear envelope, is important for doxorubicin efficiency and can be achieved with appropriately shaped nanoparticles.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalNature Nanotechnology
Volume12
Issue number1
DOIs
Publication statusPublished - 10 Jan 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature.

Funding

E.H. is funded by a Cancer Institute NSW Early Career Fellowship (RG151879) and UNSW Vice Chancellor Research Fellowship. B.K. acknowledges the Scientific and Technological Research Council of Turkey (TUBITAK) for financial support. C.B. is funded by a Future Fellowship (FT1210096) from Australian Research Council (ARC). K.G. acknowledges funding from the ARC Centre of Excellence in Advanced Molecular Imaging (CE140100011) and National Health and Medical Research Council of Australia (1059278, 1037320). J.J.G. acknowledges funding from the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (CE140100036), the ARC Laureate Fellowship (FL150100060) program and a National Health and Medical Research Council program grant (1091261). The authors thank C. Benzing (UNSW) for discussion on cell uptake and endosomal escape. The authors thank E. Gratton (University of California, Irvine) for discussion on data analysis. The work was supported by the BioMedical Imaging Facility at UNSW. E.H. is funded by a Cancer Institute NSW Early Career Fellowship (RG151879) and UNSW Vice Chancellor Research Fellowship. B.K. acknowledges the Scientific and Technological Research Council of Turkey (TUBITAK) for financial support. C.B. is funded by a Future Fellowship (FT1210096) from Australian Research Council (ARC). K.G. acknowledges funding fromthe ARC Centre of Excellence in AdvancedMolecular Imaging (CE140100011) and National Health and Medical Research Council of Australia (1059278, 1037320). J.J.G. acknowledges funding from the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (CE140100036), the ARCLaureate Fellowship (FL150100060) programand a National Health andMedical Research Council program grant (1091261). The authors thank C. Benzing (UNSW) for discussion on cell uptake and endosomal escape. The authors thank E. Gratton (University of California, Irvine) for discussion on data analysis. The work was supported by the BioMedical Imaging Facility at UNSW.

FundersFunder number
ARC Centre of Excellence in Advanced Molecular ImagingCE140100011
ARC Centre of Excellence in AdvancedMolecular Imaging
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
BioMedical Imaging Facility
National Health and Medical Research Council of AustraliaCE140100036, FL150100060
TUBITAKFT1210096
UNSW Vice Chancellor
University of California, Irvine
Australian Research Council
National Health and Medical Research Council1091261, 1037320, 1059278
Cancer Institute NSWRG151879
University of New South Wales
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu

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