Tuning payload delivery in tumour cylindroids using gold nanoparticles

Abstract

Nanoparticles have great potential as controllable drug delivery vehicles because of their size and modular functionality. Timing and location are important parameters when optimizing nanoparticles for delivery of chemotherapeutics. Here, we show that gold nanoparticles carrying either fluorescein or doxorubicin molecules move and localize differently in an in vitro three-dimensional model of tumour tissue, depending on whether the nanoparticles are positively or negatively charged. Fluorescence microscopy and mathematical modelling show that uptake, not diffusion, is the dominant mechanism in particle delivery. Our results indicate that positive particles may be more effective for drug delivery because they are taken up to a greater extent by proliferating cells. Negative particles, which diffuse more quickly, may perform better when delivering drugs deep into tissues. An understanding of how surface charge can control tissue penetration and drug release may overcome some of the current limitations in drug delivery.

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Figure 1: Schematic showing the delivery of payload by gold nanoparticles.
Figure 2: Fluorescence calibration and cellular uptake and release of FITC–AuNPs.
Figure 3: Release of FITC–SH from AuNPs in tumour cylindroids.
Figure 4: Doxorubicin release in cylindroids.
Figure 5: Effect of surface charge on diffusivity through extracellular matrix material.
Figure 6: Rate constants of cellular uptake and predictions of particle and ligand distribution in tumours.

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Acknowledgements

The authors gratefully acknowledge financial support from the National Institutes of Health (grant nos 1R21CA112335-01A and 1R01CA120825-01A1) and the National Science Foundation (grant no. DMI-0531171).

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N.F. and V.R. conceived and designed the experiments. B.K., G.H., B.T. and C.K. performed the experiments. G.H. synthesized the FITC nanoparticles. C.K. synthesized the DOX nanoparticles. B.K. performed all cell and cylindroid experiments with FITC nanoparticles and wrote all mathematical models. B.T. performed all cylindroid and cell experiments with DOX nanoparticles. B.K., B.T. and N.F. analysed the data. V.R. contributed materials. B.K. and N.F. co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Neil S. Forbes.

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The authors declare no competing financial interests.

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Kim, B., Han, G., Toley, B. et al. Tuning payload delivery in tumour cylindroids using gold nanoparticles. Nature Nanotech 5, 465–472 (2010). https://doi.org/10.1038/nnano.2010.58

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