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p. 25-26 / OVERVIEW ON PEPTIDES
Peptides as targeting agents in nano-architectures for drug delivery
CHRIS GOTHARD
Marketing Director, CPC Scientific Inc.

KEYWORDS: Peptide therapeutics, nano-architectures, drug delivery, targeting peptides, RGD peptide.

As investigation into drug delivery platforms for cancer therapeutics continues, more emphasis is being directed towards localization, cellular uptake, and targeting of cancer tissues. Conventional chemotherapy relies on compounds that target rapidly dividing cells like those found in tumor tissues, the bone marrow, immune system, hair follicles, and digestive tract. This inability to distinguish between cancer and healthy cells is a serious drawback of chemotherapy and is associated with commonly known side effects. In addition, cancer cells in tumors are often more protected by the tissues of the solid tumors making passage across the cellular membrane difficult since polar molecules interacted better with charged surface of the phospholipid bilayer of the cell (1). Drugs like Paclitaxel and Camptothecin are lethal to cancer cells but suffer from poor aqueous solubility and low bioavailability making it impossible to administer them intravenously. Efforts to formulate water soluble versions of these drugs has resulted in a change of their physiological properties, loss of antitumor activity, and changes in toxicological profiles (2-4).

BIOMOLECULES, NANOARCHITECTURES AND CELL RECEPTORS
One method to facilitate drug delivery is by integrating bio-molecules into various nano-architectures to target cancer cells with heavily over-expressed transmembrane receptors such as integrin proteins.  Of greater significance is a targeting agent that seeks out metastatic cells that have spread beyond the original site of infection and are aggressively invading new tissues. Since effective methods to modulate the pore openings in bacteria to construct nano-devices (e.g, nano-valves) (5), is progressing efficiently, investigation into bio-recognition and cellular receptor mediated endocytosis is under investigation to concentrate particles inside cancer cells both in vitro and in vivo.
Nanoparticles composed of silica, gold, dendrimers, and polymer assemblies attached to targeting peptides have been the focus in developing novel therapeutics to treat diseases like cancer, diabetes, and growth hormone deficiency. Flamel’s Medusa™ drug delivery system consists of a specially-designed amphiphilic polymers made of glutamic acid and alpha tocopherol (Vitamin E). These polymers form stable hydrogels in water and contain hydrophobic nanodomains of vitamin E and hydrophilic domains of polyglutamate. The hydrogels are capable of holding unaltered drug substances (peptides, proteins, and small molecules) and controlled dose release for up to one week.

MAKING GOOD TARGETING MOLECULES
Peptides make good targeting molecules for nanoparticles because they can be covalently attached to the surface of the particles and are relatively easy to assemble.  Companies like CPC Scientific routinely prepare custom peptides for researchers that are specifically designed to attach to nanoparticles that target various organelles, the nucleus, and receptors in the cell membrane. RGD (arginine-glycine-aspartic acid) is a specific example of a cell-targeting peptide (CTPs) (6), an interesting group of biologically significant molecules that have emerged as effective...In order to continue reading this article please register to our website – registration is for free and no fees will be applied afterwards to download contents.

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