Exploring Diffusion and Cellular Uptake: Charged Gold Nanoparticles in an in Vitro Breast Cancer Model

Gold nanoparticles have emerged as a prominent tool in nanomedicine, particularly for applications in cancer diagnostic and treatment. One of the challenges for the successful implementation of gold nanoparticles in cancer therapy is their delivery to the specific cancer area within the tumor microenvironment. The presence of cancer enables a poorly organized vascularization system, increasing the pressure with the microenvironment, limiting the uptake of particles. The physicochemical properties of the gold nanoparticles (size, shape, and surface charge) also have a significant effect on diffusion to the tumor site and cellular uptake. In this work, we analyzed the transport of 10 nm gold nanoparticles with different surface charges (neutral, negative, and positive) through a hydrogel composite. Three-dimensional in vitro models composed of breast cancer cells loaded in the hydrogel composite were used for the qualitative and quantitative evaluation of cellular uptake of the gold nanoparticles. Surprisingly, an inverse correlation between the diffusion coefficients of the nanoparticles and cellular uptake was demonstrated. Positively charged gold nanoparticles displayed high cellular uptake, although their diffusion coefficient indicated slow transport through the hydrogel matrix. Neutral particles, on the other hand, displayed fast diffusion but the lowest cellular uptake. The results obtained indicate that nanoparticle diffusion and cellular uptake should be studied together in realistic in vitro models for a true evaluation of transport in tumor microenvironments.