Novel Anticancer Drug Delivery System Utilizes DNA-Based Nanocapsules

To prevent these, doctors may limit the amount of DOX given to each patient so that the total amount a patient receives over her or his entire lifetime is 550 milligrams per square meter, or less. Furthermore, the necessity to stop treatment to protect the patient from heart disease may diminish the usefulness of DOX in treating cancer.

To counter the problem of DOX toxicity investigators at the University of North Carolina (Chapel Hill, USA) and North Carolina State University (Raleigh, USA) developed a novel DNA-based system that delivered the drug directly to cancer cells in a form that was harmless to normal tissues.

In the "nano-cocoon" system, DOX was sequestered inside a nanocapsule (cocoon) assembled from a long-chain single-stranded DNA molecule synthesized by the rolling-circle amplification (RCA) method. Multiple GC-pair sequences were integrated into the DNA chain to enhance the loading capacity for DOX. In addition to DOX, the core of the cocoon was loaded with the negatively charged enzyme DNase I, which was encapsulated in a positively charged acid-degradable polymeric nano-gel. The outside of the nano-cocoon was highlighted with folic acid residues to encourage cancer cell binding.

Following uptake of the nano-cocoon by a cancer cell, the acidic environment inside the cell caused the nano-gel to disintegrate, which released the DNase I. The activity of this enzyme degraded the structure of the nano-cocoon, which liberated the DOX to kill the cancer cell.

“This drug delivery system is DNA-based, which means it is biocompatible and less toxic to patients than systems that use synthetic materials,” said senior author Dr. Zhen Gu, assistant professor in the joint biomedical engineering program at North Carolina State University and the University of North Carolina. “This technique also specifically targets cancer cells, can carry a large drug load, and releases the drugs very quickly once inside the cancer cell. We are preparing to launch preclinical testing now. We are very excited about this system and think it holds promise for delivering a variety of drugs targeting cancer and other diseases.”

A complete description of the nano-cocoon drug delivery system was published in the October 13, 2014, online edition of the Journal of the American Chemical Society.

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