Optimizing gold nanoparticles for better medical imaging, drug delivery, and cancer therapy

Health care professionals use tiny particles of gold (nanoparticles) for a variety of medical applications — from diagnostic imaging to cancer treatment. Gold works well for these applications because it doesn’t cause adverse reactions inside the body, it doesn’t break down easily, and it’s easy to see on imaging tests.

Ontario researchers used the Canadian Light Source at the University of Saskatchewan to determine whether the size of gold nanoparticles affects how they interact with an amino acid called L-cysteine. L-cysteine plays a key role in many biological processes inside the human body. It can prevent gold nanoparticles from clumping together, which is important for ensuring medical treatments work properly. L-cysteine can form a strong bond with gold, which in turn enables it to more easily attach to specific targets, such as cancer cells.

Yolanda Hedberg, a professor of chemistry at Western University, says that while many different sizes of gold nanoparticles are used in medicine, little is known about how size affects their performance. “We’re trying to understand what they do in the body and where they go. It is important to know if the (gold) particle stays the same size, because each size has specific properties and you design the particle in this way, and then don’t want it to change in the human body.”

Using ultrabright synchrotron light — combined with other techniques — Hedberg and her team discovered that smaller gold nanoparticles (5 nanometer) bond more strongly with L-Cysteine than larger ones (10, 15, and 20 nm). For reference, a human hair is about 100,000 nm wide.

They also found that the smallest gold nanoparticles didn’t clump together as much when L-Cysteine was present. Clumping can negatively affect the effectiveness, stability, and safety of nanoparticles. “This shows they can maintain their size and properties in a biological environment,” says Hedberg.

Read more on CLS website

Molecular movie of gold nanoparticle oscillations driven by displaced electrons

Photocatalysis, sensors, solar cells: Plasmons promise a variety of applications if the processes triggered by optical excitation in the nanoparticles can be controlled. A research team from Hamburg and Berlin reports experimental observations of a so-called molecular movie that cannot be explained by established models in Nano Letters. The team including researchers from DESY provides a new theoretical model that explains the dynamics of excited gold nanoparticles observed in their experiments.

Plasmons are collective electron oscillations associated with highly localised fields. The decay of these oscillations after optical excitation is currently the subject of intense debate. Researchers assume that very energetic “hot” electrons are generated in the process which lose their energy by electron-electron scattering into a “warm” electron gas. The gas heats up the particle which eventually releases the excess energy into the environment. The efficiency of the energy transfer between the “hot electron”, “warm electron”, and “warm particle” stages is important for applications wanting to make use of these processes. In particular, the energy transfer from the warm electron gas to the nanoparticle appears to be so efficient that the particle is heated extremely quickly. In the process, it expands explosively, causing it to oscillate collectively, like a breathing sphere. However, so far direct experimental studies resolving the breathing oscillation have been missing.

For their study, researchers from the Departments of Physics and Chemistry at Universität Hamburg, the Max Planck Institute for the Structure and Dynamics of Matter (MPSD), the CFEL at DESY, and TU Berlin joined forces. Led by Holger Lange, Jochen Küpper, and Kartik Ayyer, who all conduct research in the Cluster of Excellence “CUI: Advanced Imaging of Matter”, and Andreas Knorr from Berlin, the team combined theory and experiment for an accurate description of the dynamics of excited gold nanoparticles.

Using single-particle X-ray diffractive imaging (SPI), performed at DESY’s FLASH facility, and transient absorption spectroscopy (TA), the researchers determined both the structural size and the electron temperature of the nanoparticles after optical excitation as a function of time. They observed that the particles already expanded with the optical excitation pulse, much faster than previously assumed. This observation directly proved the need for an immediate excitation source other than the temperature rise and associated expansion of the particle.

Read more on the DESY website

Image: Optical excitation of gold nanoparticles directly sets the particle into an oscillatory motion in which the particle periodically expands and contracts.

Credit: Univ. Hamburg/H. Lange

Arranging gold nanoparticles precisely in three dimensions

Metal nanoparticles have a wide variety of applications many of which stem from the fact that extremely small particles a few nanometres to  10’s of nanometres in diameter can have very different properties from those of the same material at a larger scale (a nanometre is just a billionth of a metre). Such particles are used as catalysts, coloring agents and can even  make antibacterial coatings. Some effects are due to the pattern of the particles and the spacing between them, but these are very difficult to control and particles are typically used in solution where they randomly move around like motes of dust in the air.   

In the current work, scientists based at the Bionanoscience and Biochemistry Laboratory at the Malopolska Centre of Biotechnology (MCB), Jagiellonian University showed that an artificial protein structure, a hollow sphere called a TRAP-cage, was able to act as a scaffold and provide regular-spaced points of attachment for small gold nanoparticles. “TRAP-cage is itself tiny, but at around 15 nm in diameter is still big enough to attach multiple  gold nanoparticles” explained Jonathan Heddle the head of the lab, “The protein cage is made of 12 rings, so overall it looks a little like a 12-sided dice – a dodecahedron.”  The researchers showed that there are spaces equivalent to the corners of the dodecahedron that offer just the right environment to snugly fit the gold nanoparticles inside. As a result, instead of randomly floating around, the particles appear to be constrained into a fixed three-dimensional pattern. It is hoped that the ability to arrange metal nanoparticles in this way may be developed further to produce new materials with useful properties.

Read more on the SOLARIS website

Image: The structure of the protein cage (purple) with three of the embedded gold nanoparticles highlighted (yellow) 

Credit: Jonathan Heddle

A clear path to better insights into biomolecules

An international team of scientists, led by Kartik Ayyer from the Max Planck Institute for the Structure and Dynamics of Matter, Germany, has obtained some of the sharpest possible 3D images of gold nanoparticles, and the results lay the foundation for getting high resolution images of macromolecules. The study was carried out at European XFEL’s Single Particles, Clusters, and Biomolecules & Serial Femtosecond Crystallography (SPB/SFX) instrument and the results have been published in Optica.

Carbohydrates, lipids, proteins, and nucleic acids, all of which populate our cells and are vital for life, are macromolecules. A key to understanding how these macromolecules work lies in learning the details about their structure. The team used gold nanoparticles, which acted as a substitute for biomolecules, measured 10 million diffraction patterns and used them to generate 3D images with record-breaking resolution. Gold particles scatter much more X-rays than bio-samples and so make good test specimens. They are able to provide lot more data and this is good for fine-tuning methods that can then be used on biomolecules.

Read more on the European XFEL website

Image: Illustration of 3D diffraction pattern of octahedral nanoparticles obtained by combining many snapshots after structural selection.

Credit: Kartik Ayyer and Joerg Harms, Max Planck Institute for the Structure and Dynamics of Matter