Ongoing cancer research demonstrates not only the incredible potential of nanotechnology for cancer research, but also its many versatile applications. Though nanotechnology is still a relatively young area of research, significant breakthroughs since the 1980s has propelled its applications not only to a number of fields, but also to a variety of approaches for a single problem. In 2018, cancer researchers advanced cancer research using nanotechnology to improve imaging for early detection, to reconstitute specific genes for tumour suppression, and to improve tumour targeting for diagnosis and treatment.

 

MRI Imaging

The World Health Organization recommends early detection to improve survival rates for cancer, and nanotechnology continues to advance these screening efforts by acting as a contrast agent for magnetic resonance imaging (MRI). Traditional imaging methods like gadolinium-based contrast agents (GBCA) present physical dangers to patients, including reducing kidney function with a condition known as nephrogenic systemic fibrosis. In comparison, nanotechnology presents a much lower risk than GBCA while still improving MRI visibility for cancer detection via their magnetic activity.

Currently, the A*STAR Institute of Material Research and Engineering in Singapore is developing a biocompatible peptide-coated iron oxide nanoparticle to act as a contrast agent for MRI cancer detection. While certainly safer, nanoparticles present other obstacles for imaging cancer: primarily, their tendency to degrade or adhere to other substances within the biological system, and thus reduce MRI visibility. Initially, A*STAR typically worked with silver or gold nanoparticles but this significantly limited the range of chemicals that could be used to stabilize the nanoparticle and prevent its biological breakdown. While switching to iron oxide meant that “we had to go back to the drawing board” for the peptide coating, according to project head David Paramelle, it ultimately reduces breakdown and delivers a stronger contrast agent.

Thus far, the peptide-coated iron oxide nanoparticle is testing best with liver cancer detection according to early experiments with mice and it is even outperforming commercially available contrast agents.  The team at A*STAR hopes to expand its applications to other forms of cancer detection in the near future.

Restoring Tumour Suppressors

Researchers from the Memorial Sloan Kettering Cancer Center, and in partnership with several Harvard-affiliated hospitals, are utilizing nanotechnology to reintroduce specific tumour suppressant genes for prostate cancer treatment. In particular, the phosphatase and tensin homolog (PTEN) gene helps regulate the cell cycle and prevent cells from dividing too rapidly. Many cancers, and approximately half of the metastatic castration-resistant prostate cancers observed by the research group, revealed the loss or mutation of this specific cell regulation gene. Without PTEN, cancer cells divide quickly, tumours grow, and the cancer is liable to metastasize.

To restructure and reintroduce PTEN, researchers developed messenger RNA (mRNA) nanoparticles to infiltrate abnormal cells and restore the genetic information responsible for suppressing tumour growth. So far, mouse trials have proven promising by significantly reducing tumour growth and prostate cancer progression. Moreover, mice showed no significant side effects from the treatment. Co-author of the study, Dr. Bruce R. Zetter, describes the process as a more defensive approach that “makes the tumour cell more like a normal cell, less likely to grow out of control.

Targeting Tumours for Drug Delivery

In 2005, Dr. Ulrich Wiesner’s team at the Materials Science & Engineering Department in Cornell University developed a functional core-shell silica nanoparticles called C dots (Cornell Dots). Today, the group is working on new applications for C dots targeting cancer cells with antibody fragments for both diagnostics and drug therapy purposes – the combination of which is commonly known as theranostics. In a joint effort with the Sloan Kettering Institute for Cancer Research, Wiesner’s team and researchers Dr. Feng Chen and Dr. Kai Ma improved the target specificity of C dots using favourable antibody fragments while still minimizing the size of the drug delivery vehicle.

The team focused on the anti-human epidermal growth factor receptor 2 positive (HER2+), which is a protein gene that has been significantly associated with more aggressive and less treatable breast cancer in patients. The HER2+ gene is particularly difficult to image and diagnose early using conventional methods, such as positron-emission tomography (PET) imaging, due to risks of prolonged blood circulation half-lives, inefficient tumour penetration that may irradiate healthy tissue, and days of delay for the high-contrast imaging to be complete.

This new generation of C dots, called Cornell prime dots or C’ dots, is only 6-7 nanometers wide and can therefore filter through the kidney with little irradiation. Most importantly, C’ dots are improving tumour-targeting efficiency for diagnostic efforts and drug delivery. Dr. Michelle Bradbury from Sloan Kettering calls the C’ dot a “game changer” that “could specifically deliver a variety of small molecule therapies – chemotherapy, inhibitors, and radiotherapy – without the toxicity typically found using larger particle probes.”

So far, mouse trials targeting the HER2+ cancer cells have been successful with 17.2% penetrating the tumour – a significant percentage considering the many biological competitors inadvertently accumulating the injected nanoparticles.

These scientific investigations attest to the versatility and great potential of nanotechnology applications for modern cancer research. While there is still much to discover about the ways in which nanotechnology can be practically applied, and many obstacles that have yet to be overcome in its usage, researchers continue to develop innovative techniques for more effective imaging, diagnosis, and treatment of cancerous cells. For many research groups, the next steps in these proof-of-concept studies are to improve efficacy, reduce adverse symptoms, increase cost efficiency, facilitate manufacturing processes, and target applications to more types of cancers.

 

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