Abstract
In order to maximize the potential of nanoparticles (NPs) in cancer imaging and therapy, their mechanisms of interaction with host tissue need to be fully understood. NP uptake is known to be dramatically influenced by the tumor microenvironment, and an imaging platform that could replicate in vivo cellular conditions would make big strides in NP uptake studies. Here, a novel NP uptake platform consisting of a tissue-engineered 3D in vitro cancer model (tumoroid), which mimics the microarchitecture of a solid cancer mass and stroma, is presented. As the tumoroid exhibits fundamental characteristics of solid cancer tissue and its cellular and biochemical parameters are controllable, it provides a real alternative to animal models. Furthermore, an X-ray fluorescence imaging system is developed to demonstrate 3D imaging of GNPs and to determine uptake efficiency within the tumoroid. This platform has implications for optimizing the targeted delivery of NPs to cells to benefit cancer diagnostics and therapy.
Highlights
Solid cancers are composed of cancer foci within a reactive stroma, which is populated by non-cancer cells such as fibroblasts and endothelial cells
We have developed a novel non-destructive X-ray fluorescence (XRF) technique that can be used to improve on NP imaging capabilities lacking in current systems
X-ray microanalysis confirmed gold presence within the cells; this involved a Transmission Electron Microscopy (TEM) technique that bombarded the sample with electrons and detected the emitted X-rays
Summary
Solid cancers (malignant tumors) are composed of cancer foci within a reactive stroma, which is populated by non-cancer cells such as fibroblasts and endothelial cells. The relative constituents vary, resulting in the architectural heterogeneity typical of cancer. This cancer-stromal relationship is easy to observe histopathologically in the tissues. Nanoparticles (NPs) have the potential to act as tumorspecific markers to enhance the resolution of current imaging platforms. Given their relative biologically inert qualities and stability, and unique physicochemical properties, GNPs are good contenders for enhancing imaging sensitivity. They are a reliable contrast medium for use with X-rays due to the
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