Reaching the Tumor: Mobility of Polymeric Micelles Inside an In Vitro Tumor-on-a-Chip Model with Dual ECM

• DOI: 10.1021/acsami.3c12798
• Publication Date: 2023-12-16T03:27:08Z
• Authors: Alis R. Olea; Alicia Jurado; Gadi Slor; Shahar Tevet; Silvia Pujals; Victor R. De La Rosa; Richard Hoogenboom; Roey J. Amir; Lorenzo Albertazzi
• Keywords: Nanocarriers; Acrylic acid

Degradable polymeric micelles are promising drug delivery systems due to their hydrophobic core and responsive design. When applying micellar nanocarriers for tumor delivery, one of the bottlenecks encountered in vivo is tissue barrier: crossing dense mesh cells extracellular matrix (ECM). Sometimes overlooked, can trap nanoformulations based on charge, size, hydrophobicity. Here, we used a simple design microfluidic chip with two types ECM MCF7 spheroids allow "high-throughput" screening interactions between biological interfaces micelles. To demonstrate applicability chip, small library fluorescently labeled varying hydrophilic shell forming blocks was studied. Three widely shells were tested compared, namely, poly(ethylene glycol), poly(2-ethyl-2-oxazoline), poly(acrylic acid), along enzymatically degradable dendritic cores (based hexyl or nonyl end groups). Using ratiometric imaging unimer:micelle fluorescence FRAP inside model, obtained local assembly state dynamics chip. Notably, observed different micelle behaviors basal lamina ECM, from avoidance structure binding acid) formulations. Binding correlated higher uptake into spheroids. Overall, proposed containing dual assessment evaluating nanoformulations' capacity cross barrier.