Measuring nanoparticle penetration through bio-mimetic gels

Background: In cancer nanomedicine, drugs are transported by nanocarriers through a biological system to produce a therapeutic effect. The efficacy of the treatment is affected by the ability of the nanocarriers to overcome biological transport barriers to reach their target. In this work, we focus on the process of nanocarrier penetration through tumour tissue after extravasation. Visualising the dynamics of nanocarriers in tissue is difficult in vivo, and in vitro assays often do not capture the spatial and physical constraints relevant to model tissue penetration. Methods: We propose a new simple, low-cost method to observe the transport dynamics of nanoparticles through a tissue-mimetic microfluidic chip. After loading a chip with triplicate conditions of gel type and loading with microparticles, microscopic analysis allows for tracking of fluorescent nanoparticles as they move through hydrogels (Matrigel and Collagen I) with and without cell-sized microparticles. A bespoke image-processing code- base written in MATLAB allows for statistical analysis of this tracking, and time-dependent dynamics can be determined. Results: To demonstrate the method, we show size-dependence of transport mechanics can be observed, with diffusion of fluorescein dye throughout the channel in 8 h, while 20 nm carboxylate FluoSphere diffusion was hindered through both Collagen I and Matrigel™. Statistical measurements of the results are generated through the software package and show the significance of both size and presence of microparticles on penetration depth. Conclusion: This provides an easy-to-understand output for the end user to measure nanoparticle tissue penetration, enabling the first steps towards future automated experimen- tation of transport dynamics for rational nanocarrier design.