09/22/2017

Cancer Research,cancer-fighting drugs Wisconsin team solved this problem using nanoparticles

By Live Dr - Sat Apr 11, 5:31 pm

Nanoparticles

A team of investigators at Brown University has developed a novel way to treat a class of breast cancer cells. The team has created twin nanoparticles that specifically targets the Her-2 tumor cell and unload a cancer-fighting drug directly into it. The result is a boost in antitumor activity while minimizing side effects. The findings of this study have been published in the Journal of the American Chemical Society.

Breast cancer patients face many horrors, including those that arise when fighting the cancer itself. Medications given during chemotherapy can have wicked side effects, including vomiting, dizziness, anemia, and hair loss. These side effects occur because medications released into the body target healthy cells as well as tumor cells.

The trick becomes how to deliver cancer-fighting drugs directly to the tumor cells. Brown University chemists think they have an answer: They have created twin nanoparticles that specifically target the Her-2-positive tumor cell, a type of malignant cell that affects up to 30% of breast cancer patients.

“Like a missile, you don’t want the anticancer drugs to explode everywhere,” explained Shouheng Sun, Ph.D., the study’s lead investigator. “You want it to target the tumor cells and not the healthy ones.”

The researchers created the twin nanoparticle by binding one gold nanoparticle with an iron oxide (Fe3O4) nanoparticle. On one end, they attached a synthetic protein antibody to the iron oxide nanoparticle. On the other end, they attached cisplatin to the gold nanoparticle. Visually, the whole contraption looks like an elongated dumbbell, but it may be better to think of it as a vehicle, equipped with a very good global positioning system (GPS), that is ferrying a very important passenger.

In this case, the GPS comes from the iron oxide nanoparticle, which homes in on a Her-2 breast cancer cell like a guided missile. The attached antibody is critical, because it binds to the antigen, a protein located on the surface of the malignant cell. Put another way, the nanoparticle vehicle “docks” on the tumor cell when the antibody and the antigen become connected. Once docked, the vehicle unloads its “passenger,” the cisplatin, into the malignant cell.

In a neat twist, the Brown-led team used a pH-sensitive covalent bond to connect the gold nanoparticle with the cisplatin to ensure that the drug was not released into the body but remained attached to the nanoparticle until it was time for it to be released into the malignant cell. In laboratory tests, the gold-iron oxide nanoparticle combination successfully targeted the cancer cells and released the anticancer drugs into the malignant cells, killing the cells in up to 80% of cases. “We’ve made a Mercedes Benz now,” Dr. Sun joked. “It’s not a Honda Civic anymore.”

The research builds on previous work in Dr. Sun’s lab, where researchers created peptide-coated, iron oxide nanoparticles that, in tests with mice, successfully located a brain tumor cell called U87MG. The researchers will test the breast cancer nanoparticle system in laboratory tests with animals. They also plan to create twin nanoparticles that can release the drug via remote-controlled magnetic heating.

This study, which was supported by the National Cancer Institute’s Office of Technology and Industrial Relations, appears in the paper “Dumbbell-like Au-Fe3O4 Nanoparticles for Target-Specific Platin Delivery.” An abstract of this paper is available at the journal’s Web site

Given that cancer is ultimately a genetic disease, it has long been the hope of researchers to use gene therapy to attack tumors where they might be most susceptible.

Those prospects have taken a significant step forward with the report that a trans-European research team has developed a nanoparticle that transports antitumor genes selectively to cancer cells. The technique, which leaves healthy cells unaffected, could offer hope to people with difficult-to-treat cancers. Although it has so far been tested only in mice, the researchers hope for human trials in 2 years.

Reporting its work in the journal Cancer Research, the research team, headed by Georges Vassaux, Ph.D., Institute National de la Santé et de la Recherche Médicale (INSERM), used poly(propylene imine) dendrimers as carriers for the genes. This particular dendrimer forms stable complexes with DNA that only appear to fall apart when inside tumor cells. 

 

Perhaps the best way to fight cancer is to prevent it from developing in the first place, and based on newly published research from investigators at the University of Wisconsin-Madison, nanoparticles may be able to make cancer chemoprevention a reality.

Using nanoparticles made of a biocompatible polymer, the investigators were able to encapsulate a molecule isolated from green tea that triggers apoptosis and inhibits angiogenesis, two key biochemical events that could prevent cancer. Hasan Mukhtar, Ph.D., led the team that published its results in the journal Cancer Research.

One of the chief issues in chemoprevention-the use of biologically active molecules to thwart cancer before it gains a foothold in the body-is that any such agents must be exceedingly safe, since it is likely that a person at risk for cancer would need to take the chemopreventive agent on a regular basis for a long time. Because of this requirement, many investigators have been screening naturally occuring molecules for chemopreventive activity. One such molecule, the green tea component epigallocatechin-3-gallate (EGCG), has demonstrated chemopreventive potential in a wide range of in vitro and in vivo studies. However, the body rapidly degrades this compound, limiting its clinical utility.

The Wisconsin team solved this problem using nanoparticles. When the investigators loaded biocompatible polymer nanoparticles with EGCG, they boosted its cancer-preventing activity by more than tenfold. Additional experiments confirmed that this increase resulted from a significantly longer half-life for EGCG in the body. This longer half-life correlated with a reduction in serum prostate-specific antigen levels in animals with implanted human prostate tumors.

This work, which is detailed in the paper “Introducing nanochemoprevention as a novel approach for cancer control: proof of principle with green tea polyphenol epigallocatechin-3-gallate,” was supported by the National Cancer Institute. Investigators from the Albany College of Pharmacy in New York also participated in this study.

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