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Nanobiotechnology February 2015 Viewpoints

Technology Analyst: Lucy Young

Nanoparticle-Encapsulated ADCs

Why is this topic significant?

Nanotechnology has the potential to improve the efficacy of drugs by providing vehicles for targeted drug delivery. Some companies working in this area have already had success and are paving the way for others to follow.

Description

Antibody-drug conjugates (ADCs)—which have existed for 35 years—are complexes consisting of an antibody and drug, connected by a linker. ADCs—and other biologic-drug conjugates (BDCs)—have found use in cancer treatments, combining antibodies and chemotherapy drugs that medics usually administer separately. Despite the antibodies' specificity—which helps to direct the drugs to tumors—drug developers have struggled to send high concentrations of the large biologic molecules into solid tumors. Smaller ADCs that can infiltrate these tumors exist, but their half-lives are shorter than those of the ADCs with larger antibodies. In order to preserve these smaller BDCs, biotechnology start-up Blend Therapeutics—which is based in Watertown, Massachusetts—is developing polymeric-nanoparticle coatings that preserve the smaller antibodies, improving the efficacy of the therapeutic.

Blend's leading nanoparticle-encapsulated drug consists of a peptide ligand—which specifically targets a cell-surface protein that some cancer cells overexpress—and a drug that kills cells. The company has had positive results with the drug in preclinical animal tests. In January 2015, Blend raised $21 million to help it start studies to take the drug—which the company believes represents a new class of cancer drug—to the US Food and Drug Administration's (FDA's) Investigational New Drug program and then into clinical trials.

Implications

Although Blend is mostly focusing its nanoparticle-encapsulation on one particular BDC, the platform could find use for a number of biologics. Indeed, the company is looking for partners to develop further drugs based on the technology. Of course, Blend is also continuing to develop its own new BDCs, but even with $21 million, the company will need to find larger partner companies to see its drugs through to commercialization.

Impacts/Disruptions

Research into the use of nanoparticles for targeted drug delivery has intensified in recent years as the tools for manipulation of materials at the nanoscale have improved. Because of the promise of improving the efficacy of drugs, this research has spawned myriad start-ups worldwide that are attempting to commercialize their platforms. A small number of companies have had success. For example, Abraxis BioScience developed a nanoparticle-albumin-bound platform that combined with the cancer-drug paclitaxel. The FDA approved its use in 2005, and Celgene bought Abraxis in 2009 for $2.9 billion. Arguably, Abraxis's success was partly a result of using its technology with a drug that was already commercially available. Blend appears to have developed its own drug, which could slow the commercialization process. However, Abraxis has paved the way for other nanomedicine companies such as Blend to follow.

Scale of Impact

  • Low
  • Medium
  • High
The scale of impact for this topic is: Medium

Time of Impact

  • Now
  • 5 Years
  • 10 Years
  • 15 Years
The time of impact for this topic is: 10 Years

Opportunitites in the following industry areas:

Pharmaceuticals

Relevant to the following Explorer Technology Areas:

Nanoparticle Cardiac Patches

Why is this topic significant?

Cardiovascular diseases are a major and increasing global problem. According to the World Health Organization, cardiovascular diseases "are the number one cause of death globally," accounting for 30% of all deaths in 2008. Risk factors—such as obesity and smoking—increase the likelihood of cardiovascular diseases. These risk factors are on the increase as developing countries' middle classes grow and obesity problems in developed countries continue. Research is incorporating nanotechnology into cardiac patches in order to improve the treatment of these diseases.

Description

Cardiac patches could afford damaged hearts greater opportunity for recovery. Hearts contain few stem cells and the cells are unable to multiply, so the heart cannot repair after a trauma such as a heart attack. Previous research into cardiac patches includes the use of porcine material as an extracellular matrix on which to grow heart cells. Surgeons would then insert the matrix and cells into the patient. However, the patient's immune system may reject the pig material because of residual antigens on its surface. Another problem with some research into cardiac patches is the insulating effect of the material that can hinder the electrical signal that the lab-grown heart cells produce.

Researchers at the Tel Aviv University in Israel have sought to tackle these problems. To overcome the immune response, the researchers proposed using fatty tissue from the patient's own omentum—a layer of the lining that surrounds the organs in the abdomen—to create the extracellular matrix. Although the researchers stripped the fatty acid of any cells, the use of the patient's own tissue means that any residual biological molecules should not cause an immune response. The researchers then populated the matrix with gold nanoparticles in order to increase the conductivity of the structure. In their paper in the October 2014 issue of NanoLetters, the researchers described how the patch resulted in stronger contractions in the lab-grown heart cells and a lower excitation threshold—the voltage level at which a heartbeat occurs.

Implications

The researchers state that they have had positive results from preliminary animal tests, but they still need to demonstrate that the patch actually improves heart function following a trauma. They will also need to establish whether the gold nanoparticles affect the biocompatibility of the matrix. Gold is very inert and, because the gold is part of the matrix, the biocompatibility is unlikely to change. Nevertheless, more research into the toxicity of nanoparticles—including stable gold ones—is necessary.

Impacts/Disruptions

Bovine, porcine, and synthetic cardiovascular patches are commercially available to help encourage repair after heart surgery. Research in recent years has focused on using these patches to deliver stem cells to the heart. The research at the Tel Aviv University may be a step forward in making these regenerative cardiac patches commercially viable. The addition of the gold nanoparticles appears to make the heart cells perform better, which is important considering that the matrix requires the patient to undergo extra surgery. The application of nanotechnology to the cardiac patches could inspire other scientists researching regenerative medicine to investigate the potential benefits of nanotechnology.

Scale of Impact

  • Low
  • Medium
  • High
The scale of impact for this topic is: Medium

Time of Impact

  • Now
  • 5 Years
  • 10 Years
  • 15 Years
The time of impact for this topic is: 10 Years

Opportunitites in the following industry areas:

Regenerative medicine, health care

Relevant to the following Explorer Technology Areas: