How to Keep Cancer from Returning after Surgery

After surgery to remove tumors, some cancer cells can be left behind where they can grow back or spread to a new part of the body. Researchers at the University of Wisconsin-Madison have now developed a hydrogel that can be applied post-surgery to prevent or slow tumor regrowth. The gel works by releasing two compounds selected to strategically keep cancer from coming back after surgery. First is a drug called Pexidartinib, which is already in use to inhibit tumor-associated macrophages (TAMs). These are immune cells that have, for unclear reasons, “switched sides” and now contribute to creating a pro-cancer environment. As such, inhibiting these TAMs slows the growth (or regrowth) of cancer.

A microscope image of the hydrogel (teal) containing platelets with antibodies (red) and tumor-fighting drug nanoparticles (green)

The second component is made up of PD-1 antibodies, which help train T cells to recognize and attack cancer cells. These are bound to platelets for stability. Together, the two components prevent the formation of a microenvironment that’s favorable to cancer growth, and help the immune system clear out any cancer cells remaining after surgery. After its work is done, the gel is designed to biodegrade safely in the body.

The researchers tested the gel in mouse models of several different types of cancers, including colon cancer, melanoma, sarcoma, and triple negative breast cancer. The gel significantly reduced recurrence and metastasis of the cancer, and extended the survival rates of the mice – all control animals succumbed within 36 days, while survival rates ranged between 50 and 66 percent for treated mice, depending on the type of cancer.

The local application of the gel also helps prevent side effects that can arise if a drug is delivered system-wide. As such, no major side effects were seen in the test mice. Importantly, the team says that some of these cancers don’t usually respond well to immune therapy, and are prone to metastasizing, so the effectiveness of the gel treatment is encouraging.

We are really glad to see that this local strategy can work against so many different kinds of tumors, especially these non-immunogenic tumors,” said Quanyin Hu, lead researcher on the study. “We are even more glad to see this local treatment can inhibit tumor metastasis.”


Nanomicelles Are Perfect Carrier To Destroy Cancerous Cells

With the advance in nanotechnology, researchers across the globe have been exploring how to use nanoparticles for efficient drug delivery. Similar to nanoshells and nanovesicles, nanomicelles are extremely small structures and have been noted as an emerging platform in targeted therapy. Nanomicelles are globe-like structures with a hydrophilic outer shell and a hydrophobic interior. This dual property makes them a perfect carrier for delivering drug molecules.

Now a multi-disciplinary, multi-institutional team has created a nanomicelle that can be used to deliver a drug named docetaxel, which is commonly used to treat various cancers including breast, colon and lung cancer.

Modus operandi: Once injected intravenously, these nanomicelles can easily escape the circulation and enter the solid tumours.

The ideal goal for cancer therapy is destroying the cancer cells without harming healthy cells of the body, and chemotherapeutics approved for treatment of cancer are highly toxic. The currently used docetaxel is a highly hydrophobic drug, and is dissolved in a chemical mixture (polysorbate-80 and alcohol). This aggravates its toxic effects on liver, blood cells, and lungs. So, there was an urgent and unmet need to develop effective drug delivery vehicles for docetaxel without these side effects,” explains Avinash Bajaj, from the Laboratory of Nanotechnology and Chemical Biology at the Regional Centre for Biotechnology, Faridabad. He is one of the corresponding authors of the paper recently published in Angewandte Chemie.

The nanomicelles are less than 100nm in size and are stable at room temperature. Once injected intravenously these nanomicelles can easily escape the circulation and enter the solid tumours where the blood vessels are found to be leaky. These leaky blood vessels are absent in the healthy organs. “Chemical conjugation would render the phospholipid-docetaxel prodrug to be silent in the circulation and healthy organs. But once it enters the cancer cells, the enzymes will cleave the bond to activate the drug, and kill the cancer cells,” adds Dr. Bajaj.

The team tested the effectiveness of the nanomicelles in a mice breast tumour model and was found to help in tumour regression. Its toxicity was compared with the currently used FDA approved formulation and found to be less toxic. Similar promising results were seen when tested in higher model organisms including rats, rabbits and rhesus monkeys.

Copper-based Nanomaterials Kill Cancer Cells

An interdisciplinary team of scientists from KU Leuven (Belgium), the University of Bremen (Germany), the Leibniz Institute of Materials Engineering (Germany), and the University of Ioannina (Greece) has succeeded in killing tumour cells in mice using nano-sized copper compounds together with immunotherapy. After the therapy, the cancer did not return.

Recent advances in cancer therapy use one’s own immunity to fight the cancer. However, in some cases, immunotherapy has proven unsuccessful. The team of biomedical researchers, physicists, and chemical engineers found that tumours are sensitive to copper oxide nanoparticles – a compound composed of copper and oxygen. Once inside a living organism, these nanoparticles dissolve and become toxic. By creating the nanoparticles using iron oxide, the researchers were able to control this process to eliminate cancer cells, while healthy cells were not affected.

Any material that you create at a nanoscale has slightly different characteristics than its normal-sized counterpart,” explain Professor Stefaan Soenen and Dr Bella B. Manshian from the Department of Imaging and Pathology, who worked together on the study. “If we would ingest metal oxides in large quantities, they can be dangerous, but at a nanoscale and at controlled, safe, concentrations, they can actually be beneficial.

As the researchers expected, the cancer returned after treating with only the nanoparticles. Therefore, they combined the nanoparticles with immunotherapy. “We noticed that the copper compounds not only could kill the tumour cells directly, they also could assist those cells in the immune system that fight foreign substances, like tumours,” says Dr Manshian.

The combination of the nanoparticles and immunotherapy made the tumours disappear entirely and, as a result, works as a vaccine for lung and colon cancer – the two types that were investigated in the study. To confirm their finding, the researchers injected tumour cells back into the mice. These cells were immediately eliminated by the immune system, which was on the lookout for any new, similar, cells invading the body.