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

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Biology

Background:

• Single-chain polymeric nanoparticles (SCPNs) performance in biomedicine relies on conformational stability within cells.
• Current stability studies in 2D models lack relevance to the 3D tumor microenvironment.

Purpose of the Study:

• To develop and utilize a microfluidic tumor-on-a-chip model for evaluating SCPN stability and behavior in a 3D tumor milieu.
• To investigate the impact of polymer microstructure on SCPN diffusion, cellular uptake, and stability within the tumor microenvironment.

Main Methods:

• A microfluidic chip was engineered with extracellular matrix (ECM) components (Matrigel/collagen-hyaluronic acid) and MCF7 cancer cell spheroids.
• A library of SCPNs with varying microstructures was prepared and tested for ECM penetration, cellular uptake, and conformational stability.
• The 3D platform enabled assessment of SCPN behavior during ECM traversal and internalization by 3D cancer cells.

Main Results:

• All tested SCPNs effectively penetrated the ECM.
• SCPN cellular uptake and stability were significantly influenced by their microstructure.
• Glucose-based SCPNs showed the highest spheroid uptake, followed by charged SCPNs.
• Charged SCPNs adopted an open conformation, while hydrogen-bonded SCPNs maintained a folded structure within spheroids.

Conclusions:

• The 3D microfluidic tumor-on-a-chip platform provides crucial insights into SCPN stability and behavior in a physiologically relevant tumor environment.
• Understanding the interplay between polymer microstructure and SCPN stability is key for designing effective nanoparticles for targeted biomedical applications.