Researchers at UCLA have successfully manipulated nanomaterials for the creation of a new drug delivery system which promises to solve the challenge of poor water solubility of today's most promising anticancer drugs and thereby increase their effectiveness.
Poor solubility of anticancer drugs is one of the major problems in cancer therapy today because the drugs require the addition of solvents in order to be easily absorbed into the cancer cells. Unfortunately, these solvents not only dilute the potency of the drugs, but create toxicity as well.
In a paper scheduled to be published in the journal Small in June, researchers at UCLA from the California NanoSystems Institute and the Jonsson Comprehensive Cancer Center report a novel approach using silica based nanoparticles for the delivery of camptothecin (CPT) and other water-insoluble drugs into human cancer cells. The study is led by Fuyu Tamanoi, Professor of Microbiology, Immunology & Molecular Genetics and director of the Jonsson Cancer Center Signal Transduction and Therapeutics Program Area and by Jeffrey Zink, Professor of Chemistry and Biochemistry.
Tamanoi and Zink devised a method for incorporating a representative hydrophobic anticancer drug camptothecin (CPT) into the pores of the fluorescent mesoporous silica nanoparticles (FMSN) and its delivery into a variety of human cancer cells to induce cell death. The results suggest that the mesoporous silica nanoparticles might be used as a vehicle to overcome the insolubility problem of many anticancer drugs.
"Silica nanomaterials show promise for delivering camptothecin (CPT) and other water-insoluble drugs," said Tamanoi. "We have successfully loaded hydrophobic anticancer drugs into mesoporous nanoparticles and delivered them into human cancer cells to induce cell death."
"The beauty of our findings is that these nanoparticles are biocompatible, contain tubular pores and are relatively easy to modify. Additional modification by attaching a ligand against a cancer cell specific receptor can make the nanoparticles recognizable by cancer cells," said Zink.
A critical obstacle and challenge for cancer therapy is the limited availability of effective biocompatible delivery systems. Since many effective anticancer agents have poor water solubility, the development of novel delivery systems for these molecules without the use of organic solvents has received significant attention.
CPT and its derivatives are considered to be among the most effective anticancer drugs of the 21st century. Although studies have demonstrated their effectiveness against carcinomas of the stomach, colon, neck and bladder, as well as breast, small-cell lung cancer and leukemia in vitro, clinical application of CPT in humans has only been carried out with CPT derivatives that have improved water solubility.
"In order to be used on humans, current cancer therapies, such as CPT or Taxol which are poorly water soluble, must be mixed with organic solvents in order for it to be delivered into the body," said Tamanoi. "These elements produce toxic side effects and in fact decrease the potency of the cancer therapy."
The new research findings show that nanoparticles offer great potential and a promising approach to deliver therapeutic agents into targeted organs or cells and are actively developed for application in cancer therapy.
The new alternative method for drug delivery has been tested with both CPT and Taxol.
The research team's results suggest that the mesoporous silica nanoparticles may offer a solution to the problem of poor water solubility of anticancer drugs.
In addition, nanoparticles also offer the possibility to accomplish controlled release of anticancer drugs. The pores in the nanoparticles could be closed by constructing an appropriate cap structure. The ability to control the release of anticancer drugs provides silica nanoparticles with advantages over other drug delivery systems such as pegylated liposomal particles or the use of albumin based nanoparticles.
Further work is necessary to compare and contrast different methods to improve the solubility of anticancer drugs with the goal of minimizing toxic effects on healthy tissues while maintaining anti-tumor efficacy.
This research was supported by grants from the NIH and the NSF and represents the collaboration between two totally different fields: bio science and chemistry. The researchers came together because of their common interests in the identification of novel anti-cancer drugs and the potential for nano-delivery. Both Tamanoi and Zink are members of the California NanoSystems Institute (CNSI) at UCLA, which encourages cross-disciplinary collaboration to solve problems in nanoscience and nanotechnology.
UCLA's Jonsson Comprehensive Cancer Center comprises more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2006, the Jonsson Cancer Center was named the best cancer center in California by U.S. News & World Report, a ranking it has held for seven consecutive years.