posted on 2023-12-16, 03:40authored byAlis R. Olea, Alicia Jurado, Gadi Slor, Shahar Tevet, Silvia Pujals, Victor R. De La Rosa, Richard Hoogenboom, Roey J. Amir, Lorenzo Albertazzi
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 the tumor tissue barrier: crossing the dense
mesh of cells and the extracellular matrix (ECM). Sometimes overlooked,
the extracellular matrix can trap nanoformulations based on charge,
size, and hydrophobicity. Here, we used a simple design of a microfluidic
chip with two types of ECM and MCF7 spheroids to allow “high-throughput”
screening of the interactions between biological interfaces and polymeric
micelles. To demonstrate the applicability of the chip, a small library
of fluorescently labeled polymeric micelles varying in their hydrophilic
shell and hydrophobic core forming blocks was studied. Three widely
used hydrophilic shells were tested and compared, namely, poly(ethylene
glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid), along
with two enzymatically degradable dendritic hydrophobic cores (based
on hexyl or nonyl end groups). Using ratiometric imaging of unimer:micelle
fluorescence and FRAP inside the chip model, we obtained the local
assembly state and dynamics inside the chip. Notably, we observed
different micelle behaviors in the basal lamina ECM, from avoidance
of the ECM structure to binding of the poly(acrylic acid) formulations.
Binding to the basal lamina correlated with higher uptake into MCF7
spheroids. Overall, we proposed a simple microfluidic chip containing
dual ECM and spheroids for the assessment of the interactions of polymeric
nanocarriers with biological interfaces and evaluating nanoformulations’
capacity to cross the tumor tissue barrier.