Cellular Interactions of Liposomes and PISA Nanoparticles during Human Blood Flow in a Microvascular Network

• Published in: Small 2020-08, Vol.16 (33), p.e2002861-n/a
• Main Authors: Vu, Mai N., Kelly, Hannah G., Wheatley, Adam K., Peng, Scott, Pilkington, Emily H., Veldhuis, Nicholas A., Davis, Thomas P., Kent, Stephen J., Truong, Nghia P.
• Format: Article
• Language: English
• Subjects: Blood circulation; Blood flow; Blood vessels; cellular interactions; Chemical compounds; Diagnostic systems; Drug delivery systems; fresh human blood; Hemodynamics; Humans; Liposomes; Microvessels; Modulators; Nanoparticles; Nanotechnology; Pharmacology; PISA nanoparticles; Polymerization; polymerization‐induced self‐assembly; reversible addition‐fragmentation chain transfer (RAFT); Side effects
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202002861

A key concept in nanomedicine is encapsulating therapeutic or diagnostic agents inside nanoparticles to prolong blood circulation time and to enhance interactions with targeted cells. During circulation and depending on the selected application (e.g., cancer drug delivery or immune modulators), nanoparticles are required to possess low or high interactions with cells in human blood and blood vessels to minimize side effects or maximize delivery efficiency. However, analysis of cellular interactions in blood vessels is challenging and is not yet realized due to the diverse components of human blood and hemodynamic flow in blood vessels. Here, the first comprehensive method to analyze cellular interactions of both synthetic and commercially available nanoparticles under human blood flow conditions in a microvascular network is developed. Importantly, this method allows to unravel the complex interplay of size, charge, and type of nanoparticles on their cellular associations under the dynamic flow of human blood. This method offers a unique platform to study complex interactions of any type of nanoparticles in human blood flow conditions and serves as a useful guideline for the rational design of liposomes and polymer nanoparticles for diverse applications in nanomedicine. An innovative methodology to characterize cellular interactions of nanomaterials under human blood flow conditions is developed. Fresh whole human blood and an artificial microvascular network are employed for the first time. This platform is easy to set up in any lab and can be applied to future studies of any type of nanoparticles.