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Simultaneous Exposure of Different Nanoparticles Influences Cell Uptake
Isa de Boer1, Ceri J Richards1, Christoffer Åberg1
1Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Abstract:
Drug delivery using nano-sized carriers holds tremendous potential for curing a range of diseases. The internalisation of nanoparticles by cells, however, remains poorly understood, restricting the possibility for optimising entrance into target cells, avoiding off-target cells and evading clearance. The majority of nanoparticle cell uptake studies have been performed in the presence of only the particle of interest; here, we instead report measurements of uptake when the cells are exposed to two different types of nanoparticles at the same time. We used carboxylated polystyrene nanoparticles of two different sizes as a model system and exposed them to HeLa cells in the presence of a biomolecular corona. Using flow cytometry, we quantify the uptake at both average and individual cell level. Consistent with previous literature, we show that uptake of the larger particles is impeded in the presence of competing smaller particles and, conversely, that uptake of the smaller particles is promoted by competing larger particles. While the mechanism(s) underlying these observations remain(s) undetermined, we are partly able to restrain the likely possibilities. In the future, these effects could conceivably be used to enhance uptake of nano-sized particles used for drug delivery, by administering two different types of particles at the same time.
Insights
Simultaneous exposure to two nanoparticle types alters cellular uptake. Larger nanoparticles hinder smaller ones, while smaller ones promote larger ones, offering potential for improved drug delivery strategies.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cell Biology
Background:
- Nanoparticle drug delivery offers significant therapeutic potential.
- Cellular internalization mechanisms for nanoparticles are not fully understood.
- Current studies typically examine single nanoparticle types, limiting insights into complex interactions.
Purpose of the Study:
- To investigate the simultaneous uptake of two different nanoparticle types by cells.
- To understand how co-exposure affects cellular internalization of nanoparticles.
- To explore potential applications in optimizing nanoparticle drug delivery.
Main Methods:
- Utilized carboxylated polystyrene nanoparticles of two distinct sizes as a model system.
- Exposed HeLa cells to both nanoparticle types concurrently in the presence of a biomolecular corona.
- Quantified nanoparticle uptake using flow cytometry at both average and single-cell levels.
Main Results:
- Observed that larger nanoparticles impede the uptake of smaller nanoparticles.
- Demonstrated that smaller nanoparticles promote the uptake of larger nanoparticles.
- Confirmed these effects occur even with a biomolecular corona present.
Conclusions:
- Simultaneous exposure to different nanoparticle sizes significantly influences cellular uptake dynamics.
- These size-dependent competitive and cooperative interactions present novel strategies for enhancing nanoparticle drug delivery.
- Further research is needed to elucidate the precise mechanisms driving these observed uptake alterations.
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