A 3D In Vitro Cancer Model as a Platform for Nanoparticle Uptake and Imaging Investigations

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2014-10, Vol.10 (19), p.3954-3961
• Main Authors: Ricketts, Kate P. M., Cheema, Umber, Nyga, Agata, Castoldi, Andrea, Guazzoni, Chiara, Magdeldin, Tarig, Emberton, Mark, Gibson, Adam P., Royle, Gary J., Loizidou, Marilena
• Format: Article
• Language: English
• Subjects: 3D in vitro model; 3T3 Cells; Animals; Calibration; Cancer; cancer model; Cell Line, Tumor; Cellular; Gold - chemistry; gold nanoparticles; Humans; Imaging; Imaging, Three-Dimensional; In vitro testing; Metal Nanoparticles - chemistry; Mice; Microscopy, Electron, Transmission; Nanoparticles - chemistry; Nanostructure; Nanotechnology; Neoplasms - pathology; Platforms; Three dimensional; Tissue Engineering - methods; Tumor Microenvironment; Uptakes; X-ray fluorescence; X-Rays
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201400194

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. A novel 3D biomimetic tumour model and custom‐made nanoparticle imager is presented as a platform for nanoparticle uptake studies. The model comprises a dense cancer mass with stroma, each with engineerable characteristics. Cancer versus stromal cellular uptake of gold nanoparticles within the model is quantified and 3D imaged, the delineated cancer mass emitting five times more than the surrounding stroma.