Imaging Diffusion and Stability of Single-Chain Polymeric Nanoparticles in a Multi-Gel Tumor-on-a-Chip Microfluidic Device

Linlin Deng, Alis R. Olea, Ana Ortiz-Perez, Bingbing Sun, Jianhong Wang, Silvia Pujals, Anja R.A. Palmans (Corresponding author), Lorenzo Albertazzi (Corresponding author)

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Samenvatting

The performance of single-chain polymeric nanoparticles (SCPNs) in biomedical applications highly depends on their conformational stability in cellular environments. Until now, such stability studies are limited to 2D cell culture models, which do not recapitulate the 3D tumor microenvironment well. Here, a microfluidic tumor-on-a-chip model is introduced that recreates the tumor milieu and allows in-depth insights into the diffusion, cellular uptake, and stability of SCPNs. The chip contains Matrigel/collagen-hyaluronic acid as extracellular matrix (ECM) models and is seeded with cancer cell MCF7 spheroids. With this 3D platform, it is assessed how the polymer's microstructure affects the SCPN's behavior when crossing the ECM, and evaluates SCPN internalization in 3D cancer cells. A library of SCPNs varying in microstructure is prepared. All SCPNs show efficient ECM penetration but their cellular uptake/stability behavior depends on the microstructure. Glucose-based nanoparticles display the highest spheroid uptake, followed by charged nanoparticles. Charged nanoparticles possess an open conformation while nanoparticles stabilized by internal hydrogen bonding retain a folded structure inside the tumor spheroids. The 3D microfluidic tumor-on-a-chip platform is an efficient tool to elucidate the interplay between polymer microstructure and SCPN's stability, a key factor for the rational design of nanoparticles for targeted biological applications.

Originele taal-2Engels
Artikelnummer2301072
Aantal pagina's12
TijdschriftSmall Methods
Volume8
Nummer van het tijdschrift10
Vroegere onlinedatum13 feb. 2024
DOI's
StatusGepubliceerd - okt. 2024

Bibliografische nota

© 2024 The Authors. Small Methods published by Wiley-VCH GmbH.

Financiering

L.D. and A.R.O. contributed equally to the work. This work was financed by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska Curie Grant Agreement no. 765497 (THERACAT). MSc. Laura Rijns and Dr. Hailin Fu are acknowledged for discussions on the FRAP technique. Dr. Gijs ter Huurne is acknowledged for providing BTA‐NH. 2

FinanciersFinanciernummer
Horizon 2020765497

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