Monitoring of the Local Extracellular Environment Using Chiral Gold Nanoparticles.

In three-dimensional (3D)-printed tissue models, sensitive, noninvasive techniques are required to detect changes in hydrogel structure caused by cellular remodeling. We demonstrate herein that circular dichroism (CD) spectroscopy provides a reliable method for detecting hydrogel structural variations. We probe directly the plasmonic optical activity of chiral gold nanorods (c-AuNRs) embedded within the hydrogel matrix, in response to variations in the local environment. Unlike extinction spectroscopy, we found that CD features such as zero-point crossings do not get masked by the strong scattering due to the porous hydrogel structure and are therefore sensitive to changes in the refractive index of the medium, reversible swelling and deswelling of the hydrogel, and other interactions between the hydrogel and the c-AuNR surface. By culturing metastatic breast cancer cells within the 3D hydrogel nanocomposite, we demonstrate that CD can noninvasively probe the restructuring of the hydrogel. This study highlights the potential of CD spectroscopy in combination with c-AuNRs to investigate complex changes in biological or polymeric systems.