Quantitative Label-Free Chemical Imaging of PLGA Nanoparticles in Cells and Tissues with Single-Particle Sensitivity

Abstract

Nanomedicine has brought significant advancements to healthcare by utilizing nanotechnology in medicine. Despite much promise, the further development of nanocarriers for clinical use has been hindered by a lack of understanding and visualization of nano-bio interactions. Conventional imaging methods have limitations in resolution, sensitivity, and specificity. This study introduces a label-free optical approach using stimulated Raman scattering (SRS) microscopy to image poly-(lactic-co-glycolic acid) (PLGA) nanocarriers, the most widely used polymeric nanocarrier for delivery therapeutic agents, with single-particle sensitivity and quantification capabilities. A unique Raman peak was identified for PLGA ester, enabling generalized bio-orthogonal bond imaging. We demonstrated quantitative SRS imaging of PLGA nanocarriers across different biological systems from cells to animal tissues. This label-free imaging method provides a powerful tool for studying this prevalent nanocarrier and quantitatively visualizing their distribution, interaction, and clearance in vivo.

Innovative Approaches for Drug Discovery: Quantifying Drug Distribution and Response with Raman Imaging

“…Additionally, with ex vivo mouse brain slices, widespread distribution of alkyne-labeled nanoparticles was observed throughout the tissue. Most recently, Gao et al applied SRS microscopy to visualize PLGA nanoparticles with single-particle sensitivity . The authors identified a distinct ester vibration with PLGA at 1768 cm –1 that allowed label-free detection of PLGA nanoparticle distribution across different biological systems, such as macrophage cells, skin, tumors, and liver.…”