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

Alis R. Olea, Alicia Jurado, Gadi Slor, Shahar Tevet, Silvia Pujals, Victor R. De La Rosa, Richard Hoogenboom, Roey J. Amir*, Lorenzo Albertazzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)59134-59144
Number of pages11
JournalACS Applied Materials and Interfaces
Volume15
Issue number51
DOIs
StatePublished - 27 Dec 2023

Funding

FundersFunder number
ADAMA Center for Novel Delivery Systems
Horizon 2020 Framework Programme
H2020 Marie Skłodowska-Curie Actions765497
Fonds Wetenschappelijk Onderzoek
Israel Science Foundation413/22
Tel Aviv University
Universiteit Gent
Ministerio de Ciencia e InnovaciónPID2019-109450RB- I00/AEI/10.13039/501100011033

    Keywords

    • extracellular matrix
    • microfluidics
    • nanoparticle mobility
    • polymeric micelles
    • tumor-on-a-chip

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