Photothermal confocal multicolor microscopy of nanoparticles and nanodrugs in live cells

Abstract

Growing biomedical applications of non-fluorescent nanoparticles (NPs) for molecular imaging, disease diagnosis, drug delivery, and theranostics require new tools for real-time detection of nanomaterials, drug nano-carriers, and NP-drug conjugates (nanodrugs) in complex biological environments without additional labeling. Photothermal (PT) microscopy (PTM) has enormous potential for absorption-based identification and quantification of non-fluorescent molecules and NPs at a single molecule and 1.4 nm gold NP level. Recently, we have developed confocal PTM providing three-dimensional (3D) mapping and spectral identification of multiple chromophores and fluorophores in live cells. Here, we summarize recent advances in the application of confocal multicolor PTM for 3D visualization of single and clustered NPs, alone and in individual cells. In particular, we demonstrate identification of functionalized magnetic and gold–silver NPs, as well as graphene and carbon nanotubes in cancer cells and among blood cells. The potential to use PTM for super-resolution imaging (down to 50 nm), real-time NP tracking, guidance of PT nanotherapy, and multiplex cancer markers targeting, as well as analysis of non-linear PT phenomena and amplification of nanodrug efficacy through NP clustering and nano-bubble formation are also discussed.

• Blood cells
• cancer cells
• gold nanorods
• graphene
• magnetic beads
• nanoparticles
• photothermal microscopy
• toxicity

Acknowledgements

We would like to acknowledge Nanopartz, Inc. for custom conjugation of gold nanorods and Dr Mazen Juratli for help with the cells' fixation. The editorial assistance of Dr Marinelle Ringer is also acknowledged. We acknowledge the Arkansas Research Alliance Memorandum of Understanding with the Food and Drug Administration (FDA) with the focus on graphene research.

Declaration of interest

The authors declare that there are no conflicts of interest. This work was supported by grants from the National Institute of Health (R01CA131164, R01EB009230, R01EB017217, R21EB0005123, and R21CA139373), the National Science Foundation (DBI-0852737), the award from the Department of Health and Human Services, DoD TATRC program, as well as grants from the Arkansas Bioscience Institute and the Translational Research Institute at the University of Arkansas for Medical Sciences. This work was also supported by the U.S. Food and Drug Administration (award HHSF223201210189C administered through Arkansas Research Alliance). The views presented in this paper are not necessarily those of the US FDA.

Supplementary material available online

Supplemental Videos S1–S3.