The system, dubbed a "nanosponge," uses a nanoparticle-sized system to deliver the drug payload. These nanoparticles circulate in the body until they encounter the surface of a tumor cell, where they adhere to the surface and begin releasing the drug in a controllable and predictable fashion. The controlled-release nanoparticle drug-delivery system used a targeting peptide that recognized a radiation-induced cell-surface receptor. This targeting agent combined a recombinant peptide with a paclitaxel-encapsulating nanoparticle that specifically targeted irradiated tumors, thereby increasing apoptosis and tumor-growth delay. A Phage display biopanning identified Gly-Ile-Arg-Leu-Arg-Gly (GIRLRG) as a peptide that selectively recognizes GPR78, a receptor on certain tumor cells. Antibodies to GRP78 blocked the binding of GIRLRG in vitro and in vivo. The conjugation of GIRLRG to a sustained-release nanoparticle drug-delivery system increased paclitaxel concentration and apoptosis (1)
When loaded with an anticancer drug, the delivery system is three to five times more effective than direct injection at reducing tumor growth (2). The sponge acts as a three-dimensional network or scaffold. The backbone is a long-length polyester. It is mixed in solution with crosslinkers to form the polymer. The net effect is to form spherically shaped particles filled with cavities where drug molecules can be stored. The polyester is biodegradable, so it breaks down gradually in the body. As it breaks down, it releases its drug payload in a predictable fashion (2).Targeted delivery systems of this type have several basic advantages. Because the drug is released at the tumor site instead of circulating widely through the body, it should be more effective for a given dosage. It also should have fewer harmful side effects because smaller amounts of the drug come into contact with healthy tissue. Another advantage is that the nanosponge particles are soluble in water. Encapsulating the anticancer drug in the nanosponge allows the use of hydrophobic drugs that do not dissolve readily in water. Currently, these drugs must be mixed with adjuvant reagents, which potentially can reduce the efficacy of the drug or cause side effect (2).
The nanosponge is produced through fairly simple chemistry. The researchers developed simple, high-yield so-called "click chemistry" methods for making the nanosponge particles and for attaching the linkers. The drug used for the animal studies was paclitaxel, the active ingredient in the anticancer therapy Taxol. The researchers recorded the response of two different tumor types—slow-growing human breast cancer and fast-acting mouse glioma—to single injections. In both cases, they found that the delivery through nanosponges increased the death of cancer cells and delayed tumor growth compared with other chemotherapy approaches.
1. E. Harth et al. Can. Res 70 (11), 4550–4559 (2010).
2. D. Salisbury, Exploration: Research News at Vanderbilt University, June 1, 2010.