Pair correlation microscopy reveals the role of nanoparticle shape in intracellular transport and site of drug release.
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.
EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney 2052, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney 2052, Australia.|Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.
Elizabeth
E
Hinde
EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney 2052, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney 2052, Australia.|Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.
Kitiphume
K
Thammasiraphop
Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.
Hien T T
HT
Duong
Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.|Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney 2052, Australia.
Jonathan
J
Yeow
Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.|School of Chemistry, University of New South Wales, Sydney 2052, Australia.
Bunyamin
B
Karagoz
Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.|Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney 2052, Australia.
Cyrille
C
Boyer
Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.|School of Chemistry, University of New South Wales, Sydney 2052, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney 2052, Australia.
J Justin
JJ
Gooding
EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney 2052, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney 2052, Australia.|Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052, Australia.
Katharina
K
Gaus
D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D009685:Nuclear Envelope / Q000378:metabolism*; D010316:Particle Size
D004337:Drug Carriers; D004317:Doxorubicin