In the ongoing search for better ways to target anticancer drugs to kill tumors without making people sick, researchers find that nanoparticles called buckyballs might be used to significantly boost the payload of drugs carried by tumor-targeting antibodies.
In research due to appear in an upcoming issue of the journal Chemical Communications, scientists at Rice University and The University of Texas M. D. Anderson Cancer Center describe a method for creating a new class of anti-cancer compounds that contain both tumor-targeting antibodies and nanoparticles called buckyballs. Buckyballs are soccer ball-shaped molecules of pure carbon that can each be loaded with several molecules of anticancer drugs like Taxol®.
In the new research, the scientists found they could load as many as 40 buckyballs into a single skin-cancer antibody called ZME-018. Antibodies are large proteins created by the immune system to target and attack diseased or invading cells.
Previous work at M. D. Anderson has shown that ZME-018 can be used to deliver drugs directly into melanoma tumors, and work at Rice has shown that Taxol can be chemically attached to a buckyball.
"The idea that we can potentially carry more than one Taxol per buckyball is exciting, but the real advantage of fullerene immunotherapy over other targeted therapeutic agents is likely to be the buckyball's potential to carry multiple drug payloads, such as Taxol plus other chemotherapeutic drugs," said Rice's Lon Wilson, professor of chemistry. "Cancer cells can become drug resistant, and we hope to cut down on the possibility of their escaping treatment by attacking them with more than one kind of drug at a time."
Researchers have long dreamed of using antibodies like ZME-018 to better target chemotherapy drugs like Taxol, and M. D. Anderson's Michael G. Rosenblum, Ph.D., professor in the Department of Experimental Therapeutics and Chief of the Immunopharmacology and Targeted Therapy Laboratory, has conducted some of the pioneering work in this field.
"This is an exciting opportunity to apply novel materials such as fullerenes to generate targeted therapeutics with unique properties," Rosenblum said. "If successful, this could usher in a new class of agents for therapy not only for cancer, but for other diseases as well."
While it's possible to attach drug molecules directly to antibodies, Wilson said scientists haven't been able to attach more than a handful of drug molecules to an antibody without significantly changing its targeting ability. That happens, in large part, because the chemical bonds that are used to attach the drugs -- strong, covalent bonds -- tend to block the targeting centers on the antibody's surface. If an antibody is modified with too many covalent bonds, the chemical changes will destroy its ability to recognize the cancer it was intended to attack.
Wilson said the team from Rice and M. D. Anderson had planned to overcome this limitation by attaching multiple molecules of Taxol to each buckyball, which would then be covalently connected to the antibodies. To the team's surprise, many more buckyballs than expected attached themselves to the antibody. Moreover, no covalent bonds were required, so the increased payload did not significantly change the targeting ability of the antibody.
Wilson said certain binding sites on the antibody are hydrophobic (water repelling), and the team believes that these hydrophobic sites attract the hydrophobic buckyballs in large numbers so multiple drugs can be loaded into a single antibody in a spontaneous manner to give the antibody-drug agent more "bang for the buck."
"The use of these nanomaterials solves some intractable problems in targeted therapy and additionally demonstrates the increasing value of the team science approach bridging different disciplines to uniquely address existing problems," Rosenblum said.
Jade Boyd | EurekAlert!
Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen
A one-way street for salt
21.09.2018 | Julius-Maximilians-Universität Würzburg
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
21.09.2018 | Physics and Astronomy
21.09.2018 | Life Sciences
21.09.2018 | Event News