Multi‐parametric surface plasmon resonance‐based intake quantification of label‐free light‐activated nanoparticles by therapeutic limbal stem cells for corneal blindness

Abstract

Advanced therapies with combined approaches of cell and nanomedicine‐based interventions are emerging. Corneal blindness with a severe form of limbal stem cell (LSC) deficiency is an example of defect with unmet clinical need. Towards cell‐based therapy, advanced enabling technologies are needed for efficient intracellular delivery of biomolecules both for in vitro disease modeling and for in vivo interventions. For this nanomedicine creates novel possibilities as light activatable polymeric nanoparticles (NPs) hold potential for controlled on‐demand cargo delivery with control of light. In this study, we used multi‐parametric surface plasmon resonance (MP‐SPR) technique in vitro for measuring NP intake in real‐time by therapeutic LSCs. Although a variety of NPs has been described, many challenges remain, and one is related to cell uptake of the formulations. Here, three different NP formulations were analyzed, one demonstrating clearly the highest cellular intake by LSCs. Importantly, data demonstrate that the labeling of NPs significantly reduce the cellular intake highlighting the importance of label‐free administration and quantification. The MP‐SPR based approach hold high potential as a powerful non‐invasive platform to be implemented in manufacturing of therapeutic cell‐ and cargo‐based interventions. For any therapy applications, validated non‐invasive and label independent NP intake measurement systems would be important.

In Vitro Characterization and Real-Time Label-Free Assessment of the Interaction of Chitosan-Coated Niosomes with Intestinal Cellular Monolayers

“…Based on the flow cytometry results, it is apparent that the SPR responses and kinetics measured in this study during interaction of chitosomes with cell monolayers merely reflect the strength and ability of the chitosomes to interact with the cell surface, not the cell uptake efficacy, even though in earlier studies the SPR PAP responses have been shown to reflect also the cell uptake efficacy of other types of nanoparticles. 9 , 41 − 43 Nonetheless, SPR measurements have their value in providing insights on the real-time interactions of nanoparticles with cells, especially as the measurements can be performed without the use of any labels that can affect the physicochemical properties of the nanoparticles of interest or affect cell behavior. Although it might be difficult to pinpoint the actual origin for the SPR PAP responses when measuring nanoparticle interactions with cells, i.e., cell surface interaction or cell uptake of nanoparticles, the SPR PAP responses and the rate constants extracted from the results can nevertheless be related to the strength of interaction or ability of the nanoparticles to interact with cells, which consequently reflects the drug delivery efficacy or targetability of the nanoparticles of interest.…”