Researchers at UCLA have successfully manipulated nanomaterials to create a drug-delivery system that overcomes solubility problems to make modern anticancer drugs more effective.
The poor solubility of anticancer drugs is one of the major problems in cancer therapy because the drugs require the addition of solvents in order to be easily absorbed into cancer cells. Unfortunately, these solvents not only dilute the potency of the drugs but create toxicity as well.
Researchers from UCLA’s California NanoSystems Institute and Jonsson Cancer Centre have developed a novel approach using silica-based nanoparticles to deliver the anticancer drug camptothecin and other water-insoluble drugs into human cancer cells.
Fuyu Tamanoi, UCLA professor of microbiology, immunology and molecular genetics and director of the Jonsson Cancer Centre’s Signal Transduction and Therapeutics Program Area, and Jeffrey Zink, UCLA professor of chemistry and biochemistry, led the study.
Tamanoi and Zink devised a method for incorporating the representative hydrophobic anticancer drug camptothecin into the pores of fluorescent mesoporous silica nanoparticles and delivering the particles 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.
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.
Camptothecin (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 against breast cancer, 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.
To overcome having to mix the drugs with organic solvents that may have toxic side effects, drug delivery systems using pegylated polymers, liposomal particles or albumin-based nanoparticles have been developed.
The new research findings show that mesoporous silica nanoparticles offer a promising approach to the delivery of therapeutic agents into targeted organs or cells. Constructing an appropriate cap structure could close the pores in the nanoparticles. This provides the ability to control the release of anticancer drugs by external stimuli.