Antibody-Drug Delivery System Kills Cancer Cells With Extreme Precision

It sounds like the stuff of science fiction: a man-made crystal that can be attached to antibodies and then supercharge them with potent drugs or imaging agents that can seek out diseased cells with the highest precision, resulting in fewer adverse effects for the patient.

However, that is precisely what researchers from the Australian Centre for Blood Diseases at Monash University in collaboration with the TU Graz (Austria) have developed: the world’s first metal-organic framework (MOFs) antibody-drug delivery system that has the potential to fast-track potent new therapies for cancer, cardiovascular and autoimmune diseases.

Schematic illustration of the new MOF Antibody crystals and their ability to specifically seek out cancer cells to detect them and deliver highly potent drugs with unprecedented precision

The in vitro study showed that when MOF antibody crystals bind to their target cancer cells and if exposed to the low pH in the cells, they break down, delivering the drugs directly and solely to the desired area.

The metal-organic framework, a mixture of metal (zinc) and carbonate ions, and a small organic molecule (an imidazole, a colourless solid compound that is soluble in water) not only keeps the payload attached to the antibody but can also acts as a reservoir of personalised therapeutics. This is a benefit with the potential to become a new medical tool to target specific diseases with customised drugs and optimised doses.

The findings are now published in the world-leading journal Advanced Materials.


Microrobot Fish Swims Through the Body to Vomit Drugs on cancer

Delivering chemotherapy drugs directly to cancers could help reduce side effects, and soon that job could be done by tiny 3D-printed robotic animals. These microrobots are steered by magnets, and only release their drug payload when they encounter the acidic environment around a tumor.

A new microrobot fish could one day swim through the body with a mouthful of drugs, and automatically spit them up when it encounters cancer cells

The new microrobots are made of hydrogel 3D printed into the shape of different animals, like a fish, a crab and a butterfly, with voids that can carry particles. The team adjusted the printing density in specific areas, like the edges of the crab’s claws or the fish’s mouth, so that they can open or close in response to changes in acidity. Finally, the microrobots were placed in a solution containing iron oxide nanoparticles to make them magnetic.

The end result was microrobots that could be loaded up with drug nanoparticles and steered towards a target location using magnets, where they would release their payload automatically due to changes in pH levels.

In lab tests, the researchers used magnets to guide a fish microrobot through simulated blood vessels, towards a cluster of cancer cells at one end. In that area, the team made the solution slightly more acidic and the fish opened its mouth and spat out the drugs on cue, killing the cancer cells. In other tests, crab microrobots could be made to clasp drug nanoparticles with their claws, scuttle to a target location, and release them.


How To Stop Influenza Virus

The critical, structural changes that enveloped viruses, such as HIV, Ebola and influenza, undergo before invading host cells have been revealed by scientists using nano-infrared spectroscopic imaging, according to a study led by Georgia State University and the University of Georgia. The researchers found that an antiviral compound was effective in stopping the influenza virus from entering host cells during lower pH exposure, the optimal condition for the virus to cause infection.

Enveloped viruses are among the most deadly known viruses. These viruses have an outer membrane covering their genetic material, and to invade host cells enveloped viruses must first attach to a cell and then open their membrane to release genetic material. Originally, scientists believed this mechanism was controlled by the host cell. In this study, which focused on influenza virus, the researchers examined the structural changes that occur for the virus to open and release its genetic material. They conducted the experiment in the absence of cells and instead simulated the cell environment. When influenza virus infects a person’s body, it goes from a neutral environment outside the cell to a more acidic environment (a lower pH) inside the cell. To simulate the cell environment for this study, the researchers made the environment more acidic. The researchers exposed influenza virus particles to the lower pH and monitored structural changes in the virus.

What we saw is that even without the cell, if we change the environment, the virus particle will break and release the genetic material,” said Dr. Ming Luo, a senior author of the study and professor in the Department of Chemistry at Georgia State. “So it has a proactive mechanism built into the virus particle. Once the virus particle finds that the environment has changed, it will itself release the material. It doesn’t need the help of the cell membrane. It has to find a sweet spot to release the genetic material, and that sweet spot happens to have a low pH.”

The researchers used nano-infrared spectroscopy, a microscopic imaging system, to observe how influenza virus particles change when their environment changes. During his work at Georgia State, Dr. Yohannes Abate, now at the University of Georgia, adapted the imaging technology to have a new, unique function that allowed them to study virus particles in more detail.

The findings are published in the journal PLoS One.