Elucidating mechanism cellular uptake removal protein
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.
performed all cylindroid and cell experiments with DOX nanoparticles. The authors declare no competing financial interests. All authors discussed the results and commented on the manuscript. In order to engineer safer nanomaterials, there is a need to understand, systematically evaluate, and develop constructs with appropriate cellular uptake and intracellular fates.The overall goal of this project is to determine the uptake patterns of silica nanoparticle geometries in model cells, in order to aid in the identification of the role of geometry on cellular uptake and transport.
In our experiments we observed a significant difference in the viability of two phenotypes of primary macrophages; immortalized macrophages exhibited similar patterns.