Patricia Van Arnum
|
Creating or improving systems for targeted drug delivery is an area of ongoing research, and is an area of particular importance
to delivering anticancer therapeutics. Researchers at Vanderbilt University and Emory University recently reported on a controlled-release
nanoparticle drug-delivery system, which may be an improved delivery method for delivering anticancer therapies, including
direct injection into a tumor site.
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.
Sources
1. E. Harth et al. Can. Res
70 (11), 4550–4559 (2010).
2. D. Salisbury, Exploration: Research News at Vanderbilt University, June 1, 2010.
