Animal tests show Rice-developed technology effective against aggressive cancer
The first preclinical study of a new Rice University-developed anti-cancer technology found that a novel combination of existing clinical treatments can instantaneously detect and kill only cancer cells -- often by blowing them apart -- without harming surrounding normal organs.
The first preclinical study of the anti-cancer technology "quadrapeutics" found it to be 17 times more efficient than conventional chemoradiation therapy against aggressive, drug-resistant head and neck tumors.
Credit: D. Lapotko/Rice University
The research, which is available online this week Nature Medicine, reports that Rice's "quadrapeutics" technology was 17 times more efficient than conventional chemoradiation therapy against aggressive, drug-resistant head and neck tumors.
The work was conducted by researchers from Rice, the University of Texas MD Anderson Cancer Center and Northeastern University.
"We address aggressive cancers that cannot be efficiently and safely treated today," said Rice scientist Dmitri Lapotko, the study's lead investigator. "Surgeons often cannot fully remove tumors that are intertwined with important organs. Chemotherapy and radiation are commonly used to treat the residual portions of these tumors, but some tumors become resistant to chemoradiation. Quadrapeutics steps up when standard treatments fail. At the same time, quadrapeutics complements current approaches instead of replacing them."
Lapotko said quadrapeutics differs from other developmental cancer treatments in that it radically amplifies the intracellular effect of drugs and radiation only in cancer cells. The quadrapeutic effects are achieved by mechanical events -- tiny, remotely triggered nano-explosions called "plasmonic nanobubbles." Plasmonic nanobubbles are non-stationary vapors that expand and burst inside cancer cells in nanoseconds in response to a short, low-energy laser pulse. Plasmonic nanobubbles act as a "mechanical drug" against cancer cells that cannot be surgically removed and are otherwise resistant to radiation and chemotherapy.
In prior studies, Lapotko showed he could use plasmonic nanobubbles alone to literally blow cells apart. In quadrapeutics, his team is using them to detect and kill cancer cells in three ways. In cancer cells that survive the initial explosions, the bursting nanobubbles greatly magnify the local doses of both chemotherapy drugs and radiation. All three effects -- mechanical cell destruction, intracellular drug ejection and radiation amplification -- occur only in cancer cells and do not harm vital healthy cells nearby.
To administer quadrapeutics, the team uses four clinically approved components: chemotherapy drugs, radiation, near-infrared laser pulses of low energy and colloidal gold.
"Quadrapeutics shifts the therapeutic paradigm for cancer from materials -- drugs or nanoparticles -- to mechanical events that are triggered on demand only inside cancer cells," Lapotko said. "Another strategic innovation is in complementing current macrotherapies with microtreatment. We literally bring surgery, chemotherapies and radiation therapies inside cancer cells."
The first component of quadrapeutics is a low dose of a clinically validated chemotherapy drug. The team tested two: doxorubicin and paclitaxel. In each case, the scientists used encapsulated versions of the drug that were tagged with antibodies designed to target cancer cells. Thanks to the magnifying effect of the plasmonic nanobubbles, the intracellular dose -- the amount of the drug that is active inside cancer cells -- is very high even when the patient receives only a few percent of the typical clinical dose.
The second component is an injectable solution of nontoxic gold colloids, tiny spheres of gold that are thousands of times smaller than a living cell. Quadrapeutics represents a new use of colloidal gold, which has been used for decades in the clinical treatment of arthritis. In quadrapeutics, the gold colloids are tagged with cancer-specific clinically approved antibodies that cause them to accumulate and cluster together inside cancer cells. These gold "nanoclusters" do nothing until activated by a laser pulse or radiation.
The third quadrapeutic component is a short near-infrared laser pulse that uses 1 million times less energy that a typical surgical laser. A standard endoscope delivers the laser pulse to the tumor, where the gold nanoclusters convert the laser energy into plasmonic nanobubbles.
The fourth component is a single, low dose of radiation. The gold nanoclusters amplify the deadly effects of radiation only inside cancer cells, even when the overall dose to the patient is just a few percent of the typical clinical dose.
"What kills the most-resistant cancer cells is the intracellular synergy of these components and the events we trigger in cells," Lapotko said. "This synergy showed a 100-fold amplification of the therapeutic strength of standard chemoradiation in experiments on cancer cell cultures."
In the Nature Medicine study, the team tested quadrapeutics against head and neck squamous cell carcinoma (HNSCC), an aggressive and lethal form of cancer that had grown resistant to both chemotherapy drugs and radiation. Quadrapeutics proved so deadly against HNSCC tumors that a single treatment using just 3 percent of the typical drug dose and 6 percent of the typical radiation dose effectively eliminated tumors in mice within one week of the administration of quadrapeutics.
Lapotko, a faculty fellow in biochemistry and cell biology and in physics and astronomy, said he is working with colleagues at MD Anderson and Northeastern to move as rapidly as possible toward prototyping and a human clinical trial. In clinical applications, quadrapeutics will be applied as either a stand-alone or intra-operative procedure using standard endoscopes and other clinical equipment and encapsulated drugs such as Doxil or Lipoplatin. Though the current study focused on head and neck tumors, Lapotko said quadrapeutics is a universal technology that can be applied for local treatment of various solid tumors, including other hard-to-treat types of brain, lung and prostate cancer. He said it might also prove especially useful for treating children due to its safety.
"The combination of aggressiveness and drug and radiation resistance is particularly problematic in tumors that cannot be fully resected, and new efficient solutions are needed," said Dr. Ehab Hanna, a surgeon and vice chair of the Department of Head and Neck Surgery at MD Anderson, who was not involved with the testing or development of quadrapeutics. "Technologies that can merge and amplify the effects of surgery, drugs and radiation at the cellular level are ideal, and the preclinical results for quadrapeutics make it a promising candidate for clinical translation."
Study co-authors included Rice research scientist Ekaterina Lukianova-Hleb, MD Anderson researchers Xiangwei Wu and Xiaoyang Ren and Northeastern researchers Vladimir Torchilin and Rupa Sawant.
The research was supported by the National Institutes of Health, the National Science Foundation and the Virginia and L.E. Simmons Family Foundation.
VIDEO is available at: http://youtu.be/_pgH6YMby3M
High-resolution IMAGES are available for download at:
CAPTION: The first preclinical study of the anti-cancer technology "quadrapeutics" found it to be 17 times more efficient than conventional chemoradiation therapy against aggressive, drug-resistant head and neck tumors.
CREDIT: D. Lapotko/Rice University
CAPTION: Dmitri Lapotko
CREDIT: Jeff Fitlow/Rice University
CAPTION: Ekaterina Lukianova-Hleb
CREDIT: Jeff Fitlow/Rice University
A copy of the Nature Medicine paper is available at: http://dx.doi.org/10.1038/nm.3484
This release can be found online at news.rice.edu.
Follow Rice News and Media Relations via Twitter @RiceUNews.
Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,920 undergraduates and 2,567 graduate students, Rice's undergraduate student-to-faculty ratio is 6.3-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice has been ranked No. 1 for best quality of life multiple times by the Princeton Review and No. 2 for "best value" among private universities by Kiplinger's Personal Finance.
Jade Boyd | Eurek Alert!
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction