Advanced Light Source Imaging, a powerful tool for nanomedicine


In the era of biomedical applications of nanoparticles, it is imperative to determine how they affect biological functions and the future of nanomedicine. This analysis would contribute positively to optimize nanomedicine, reduce side effects, improve clinical translation and maximize its impact.

Study: Advanced light source analytical techniques to explore the biological behavior and fate of nanomedicines. Image Credit: Kateryna Kon/

The rapid growth of advanced analytical light source (ALS) technologies has enabled scientists to determine the fate of nanomedicines live. Researchers have recently reviewed ALS analytical technologies, particularly spectroscopy and imaging, to highlight their applicability in determining the biological behavior and fate of nanomedicines. This review is available in AEC Core Sciences.

Factors affecting the bioidentity of nanomedicines

Scientists have discovered many new nanomedicines that are applied in various fields of biomedicine, including drug delivery, diagnosis and therapy. Even though the applications of nanomedicine have greatly improved the efficacy of conventional drugs, researchers face various challenges related to its production, preclinical characterization and clinical outcomes.

Previous studies have revealed that the physicochemical properties of nanoparticles, i.e. size, shape and charge, determine the efficacy and fate of nanomedicines. For instance, live the formation of protein corona on the surface of the nanoparticles modifies its biodistribution and its characteristic properties, affecting the bioidentity of the nanomedicines.

The transformation of nanomedicines in the complex environment of biological systems also induces modifications of their surface properties and their function. However, the exact physicochemical behavior of nanostructured nanomedicines in the biological environment is not well understood.

Understanding complex biological functions, the relationship between a nanomaterial and a biological component (nano-bio interaction), the fate of nanomedicine and the spatio-temporal interactions between various nanoparticles is important for optimizing nanomedicines.

Information from in-depth characterization of nanomedicines could aid in the rational design of future nanomedicines that prevent oxidative stress, toxicity, surface protein corona formation, and genetic damage.

Analysis of the behavior of nanomedicine in biological environments

Several imaging techniques, such as electron microscopy, light microscopy and positron emission tomography/single photon emission computed tomography (PET/SPECT), are used to study the behavior of nanomedicines in dynamic biological environments. Although electron microscopy, which includes scanning transmission microscopy (SEM) and transmission electron microscopy (TEM), is used to capture high-resolution images, in situ imaging of the internal structure of cells or fabrics is difficult.

Fluorescence microscopy is a type of optical microscopy that allows high-resolution imaging of the dynamic behavior of nanomedicines. However, one of the limitations associated with the application of this microscopy is the lack of suitable fluorescence probes. PET/SPECT are used to image humans and small animals; however, this technique requires radiolabeled nanomaterials.

ALS Imaging and Spectroscopic Analysis to Assess Nanomedicines in Biological Environments

Recently, ALS imaging and spectroscopic technologies have been used to study nano-bio interactions. ALS imaging technology (e.g., X-rays) allows deep penetration into the sample and interaction with matter to generate fluorescence signals. Some of the major advantages of ALS technology are simple sample preparation, quantitative analysis, label-free approach, in-situ imaging, high resolution, and high penetration depth. Scientists use ALS-based technology to determine the biological behavior and fate of nanomedicine in cells or tissues in their native or semi-native state.

The authors reviewed several ALS-based X-ray microscopy and spectroscopy, including scanning transmission X-ray microscopy (STXM), full-field transmission X-ray microscopy (TXM), absorption spectroscopy X-rays (XAS) and coherent diffraction imaging. (CDI), which produce images in two or three dimensions (2D or 3D).

These analytical tools are used to determine the chemical form and morphological knowledge of nanomedicines. They also provide information on the nano-bio interaction in cells, tissues or organelles, at a resolution of a few tens of nanometers.

X-ray microscopes and spectroscopy provide 3D structure information and absorption-based spectroscopic information at nanoscale resolution. It is extremely important to continuously develop new analytical technologies based on next-generation ALS, with greater multimodal data fusion, spatial and temporal resolution and superior prediction capabilities, to fully understand the interaction of nanomedicines in biological contexts.

X-ray free electron laser (XFEL) with femtosecond pulse is a potential analytical method that allows high spatial resolution imaging with rapid and dynamic tracking of structural changes, physicochemical states and functional evolution of nanomedicines at the atomic scale.

The scientists said light and electron microscopy provide structural and cellular information, while mass spectroscopy offers molecular data. At present, the algorithm-synchronized multimodal correlative ALS microscope has become the world’s leading development of light source beamlines.

ALS-based microscopy offers detailed information on nano-bio interactions, which are correlated with changes in biological functions. These data are obtained based on simultaneous information generated from various measurement modes, for example, scattering, absorption, fluorescence, etc. The researchers said the process of simultaneously acquiring data is beneficial, unlike sequential methods, because it introduces less radiation, which minimizes damage to biological specimens.

Future prospects

Going forward, developments in next-generation ALS together with its corresponding algorithms and integrated device control systems, are needed to improve downstream quantitative imaging, especially in the context of speed and precision of 3D resolution.

The scientists said that to support clinical translation of nanomedicines, methods for sample preparation and ALS data acquisition need to be improved. This would allow rapid screening of clinical samples to assess the efficacy of nanomedicines.

The authors recommend collaboration between engineers, scientists and clinicians in the ALS beamline, which could develop a feedback loop for better clinical translation of nanomedicines.


Cao, M. et al. (2022) Advanced Light Source Analytical Techniques to Explore the Biological Behavior and Fate of Nanomedicines. AEC Core Sciences.

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