Description
One of the challenges faced in medicine regarding the treatment of cancer is the delivery and the stability of the anticancer drug to the tumor. Thus nanoparticles (NPs) offer a way to help the delivery of a specific drug but also a protection against degradation [1]. However, the lack of tumor treatment based on NPs means that we still need to develop new platforms and also new types of NPs. We work here with self-assembled lipids called cubosomes, that are a promising tool for drug delivery thanks to their capacity to be loaded with hydrophilic or hydrophobic components and their encapsulation efficiency. A crucial point is to quantify the penetration of these cubosomes in biological tissues, a necessary step to ensure their efficiency in vivo. In this study, we developed a microfluidic chip that allows the immobilization of multiple 3D cell aggregates (here A338 spheroids, murine cell line affected with pancreatic cancer). These spheroids constitute a classical in vitro 3D tissue model. The microfluidic technology is based on a previous work in the team, which was developed to reproduce the micropipette aspiration technique on a chip [2]. In parallel, the unique design of the chip allows a rapid change of media around the sample and can help understand the penetration and effect of many compounds such as cubosomes on spheroids. These cubosomes can be loaded with fluorescent molecules such as Oregon Green DHPE or DiR for direct fluorescence of cubosomes, or fluorescein-DA to detect esterase activity in cells. Preliminary results on penetration show that cubosomes loaded with Oregon Green can penetrate up to the center of the A338 spheroids. The micropipette aspiration technique can be used to perform mechanical measurements on 3D biological samples: we could measure the elasticity and viscosity of the cell line, and evidence that permeability can play a role in tissue’s deformations.
References:
[1] S. Gavas, « Nanoparticles for Cancer Therapy: Current Progress and Challenges », Nanoscale Research Letters, 2021, doi: 10.1186/s11671-021-03628-6.
[2] S. Landiech et al., « Parallel on-chip micropipettes enabling quantitative multiplexed characterization of vesicle mechanics and cell aggregates rheology ». APL Bioengineering. 12 juin 2024. doi: 10.1063/5.0193333.