Tuning payload delivery in tumour cylindroids using gold nanoparticles

We show that positively- and negativelycharged gold nanoparticles carrying either fluorescein or doxorubicin molecules move and localize differently in an in vitro three dimensional model of tumour tissue

Byoungjin Kim

2010

Scholarcy highlights

  • Nanoparticles have great potential as controllable drug delivery vehicles because of their size and modular functionality
  • Positive and negative gold nanoparticles conjugated with doxorubicin were synthesized, and our results show that surface charge can be used to control tissue penetration and drug release
  • The enhanced cellular uptake of positive particles by proliferating cells may be caused by electrostatic interaction with the net negative surface charge of the plasma membrane, which has be observed in liposomal and polymeric delivery systems
  • Using a combination of experimental in vitro tumour models and mathematical modelling, we showed that under most circumstances, positively charged nanoparticles improved delivery of payloads to the majority of cells in tumours, whereas negatively charged particles would perform better when delivering drugs deep into tissues
  • Positive particles had significantly higher uptake and dissociation by viable cells, whereas negative particles diffused faster. Both positive and negative particles penetrated tissues rapidly and for both, the rate of cellular uptake and dissociation was slower than extracellular diffusion
  • The mathematical models suggested that the rate of cellular uptake of both particles was fast in apoptotic and necrotic tissues, and the uptake kinetics of positive particles was irreversible, whereas it is reversible for negative particles over the time scales investigated
  • The ability to tune surface charge to control tissue penetration and drug release makes gold nanoparticles a flexible and powerful drug delivery vehicle

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