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

New insights to advance targeted brain cancer therapy

Despite an increase in new chemotherapies, the overall prognosis for patients with glioblastoma multiforme (GBM) remains extremely poor, with just 5% of patients surviving for more than five years. This aggressive form of brain cancer is highly resistant to treatment, prompting researchers to explore new treatment avenuesRiluzole, a drug that has already been approved by the FDA to treat amyotrophic lateral sclerosis (ALS), is currently being explored as a treatment for several cancers including GBM. However, there is a need for novel drug delivery methods to enhance riluzole’s effectiveness and overcome barriers to targeted therapy, including minimizing harmful side effects in healthy cells, and maintaining the drug’s anti-cancer efficacy until it reaches tumor cells.

In this study, which was led by Tanja Dučić, scientist in the MIRAS beamline team at the ALBA Synchrotron, and published in ACS Omegaresearchers engineered carbon-based nanoparticles, or carbon dots, made of 2-acrylamido-2-methylpropanesulfonic acid (AMPS). This organic delivery system (AMPS-CDs NPs) showed biocompatibility with glioblastoma cells, and researchers were keen to test its potential to act as a nanocarrier for the drug riluzole.

Several Spanish institutions and researchers collaborated in this project, including Manuel Algarra from INAMAT2 (Institute for Advanced Materials and Mathematics), at the Public University of Navarra; Elena Gonzalez-Munoz, Maria Soledad Pino-González and Juan Soto from the University of MalagaPablo Guerra from the Institute of Molecular Biology of Barcelona (IBMB-CSIC); and Tanja Dučić from ALBA.

The study demonstrates the successful complementarity between synchrotron light and electron microscopy. By combining the MIRAS beamline and the Cryo-TEM at IBMB-CSIC, part of the Joint Electron Microscopy Center at ALBA (JEMCA), the collaboration achieved its first publication using both instruments. Pablo Guerra, coordinator of the Cryo-TEM, performed the microscope data acquisition. “Using the Cryo-TEM we confirmed the nanoparticles’ shape and size, with a diameter of 4.5-5 nm, which was impossible to observe with other methods”, says Tanja Dučić.

The nanoparticles were extensively characterized to determine their exact surface composition using techniques that included XPS (X-ray photoelectron spectroscopy) and NMR (nuclear magnetic resonance) spectroscopy, as well as cryo-transmission electron microscopy. The synthesized nanoparticles are covered in sulfonated, carboxylic, and substituted amide groups. These functional groups make the AMPS-CDs potentially suitable nanocarriers for riluzole.

Read more on ALBA website

Image: Researchers Tanja Dučić from ALBA and Pablo Guerra from IBMB-CSIC at the control room of the EM01-Cryo-TEM of the Joint Electron Microscopy Center at ALBA

Credit: JEMCA

Nanoparticles made from marine polymers for cutaneous drug delivery applications

A research led by the University of Porto in collaboration with the ALBA Synchrotron has studied for the first time the interaction of nanoparticles with the skin, using synchrotron light at the MIRAS beamline. The findings unveil the role of the different skin components and the mechanism of the permeation enhancement conferred with nanoparticles, made from marine polymers. A nano delivery system application in the skin will reduce the dosage needed due to controlled drug delivery and allow newer and better-targeting therapeutic strategies towards cutaneous administration.

Cutaneous drug delivery allows the administration of therapeutic and cosmetic agents through the skin. Advantages of this administration route include high patient compliance, avoidance of high concentration levels of the drug when reaching systemic circulation, and far fewer side effects compared to other administration routes.

Still, the peculiar skin structure assures protection to the human organism and hampers drug delivery. To overcome this issue, skin permeation enhancers, such as nanoparticles, can be used. They are pharmacologically inactive molecules that can increase skin permeability by interacting with the stratum corneum, the first layer of the epidermis, which is the outermost layer of the skin. However, the mechanisms of nanoparticles’ interaction with the skin structure are still unknown.

A research project led by the University of Porto (Portugal) in collaboration with the ALBA Synchrotron has studied for the first time the interaction of polymeric nanoparticles with the skin, using synchrotron light.

Read more on the ALBA website

Image: Nanoparticles made visible on human skin – 3D Rendering

Credit: Adobe Stock

Delivering drugs using nanocrystals

Monash University researchers have used advanced techniques at ANSTO to investigate the production of new, elongated polymer nanocapsules with a high payload of drug nanocrystals to potentially increase drug targetability, and also decrease dosage frequency and side effects.

This method had not been investigated previously and represents a pioneering method of investigation in the field of colloidal science applications for drug delivery.

Nanoparticles have been used to increase the delivery efficiency of cancer therapy because of their biocompatibility, versatility and the easiness of functionalisation.

The team engineered novel elongated polymer nanocapsules, which are unlike the more well-known spherical nanocapsules.

The elongated polymer nanocapsules were made with elongated liposomes or surfactant vesicles and used drug nanocrystals as a template. 

The results provided strong evidence that the elongated structure could be retained, and also confirmed that the loading method to form rod-like drug nanocrystals inside liposomes was a practical solution.

The combination of the high drug payload, in the form of encapsulated nanocrystals, and the non-spherical feature of liposomes represented a more efficient delivery system.

Spherical hollow nanocapsules have been studied extensively, but the formation of elongated nanocapsules containing active pharmaceuticals as therapeutic agents has been previously largely unsuccessful. 

Read more on the ANSTO website

Image: Elongated nanocapsules can be prepared by polymerisation at the surface of elongated liposome templates with drug nanocrystals