Cell adhesion molecules for targeted drug delivery

Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, United States
Journal of Pharmaceutical Sciences (Impact Factor: 2.59). 09/2006; 95(9):1856-72. DOI: 10.1002/jps.20676
Source: PubMed


Rapid advancement of the understanding of the structure and function of cell adhesion molecules (i.e., integrins, cadherins) has impacted the design and development of drugs (i.e., peptide, proteins) with the potential to treat cancer and heart and autoimmune diseases. For example, RGD peptides/peptidomimetics have been marketed as anti-thrombic agents and are being investigated for inhibiting tumor angiogenesis. Other cell adhesion peptides derived from ICAM-1 and LFA-1 sequences were found to block T-cell adhesion to vascular endothelial cells and epithelial cells; these peptides are being investigated for treating autoimmune diseases. Recent findings suggest that cell adhesion receptors such as integrins can internalize their peptide ligands into the intracellular space. Thus, many cell adhesion peptides (i.e., RGD peptide) were used to target drugs, particles, and diagnostic agents to a specific cell that has increased expression of cell adhesion receptors. This review is focused on the utilization of cell adhesion peptides and receptors in specific targeted drug delivery, diagnostics, and tissue engineering. In the future, more information on the mechanism of internalization and intracellular trafficking of cell adhesion molecules will be exploited for delivering drug molecules to a specific type of cell or for diagnosis of cancer and heart and autoimmune diseases.

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Available from: Teruna Siahaan, Feb 12, 2015
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    • "However, the bottleneck is a lack of a suitable vector to provide an optimal delivery system and achieve efficient knockdown effects at the target site.20 It has been reported that several integrin receptors are overexpressed on the surface of retinal pigment epithelial cells in ocular neovascularization.21–25 Thus, a gene vector with the ligand of the integrin receptor, such as an Arg-Gly-Asp (RGD) moiety containing peptide, could be used for specific delivery of anti-VEGF siRNA to retinal pigment epithelial cells and prevent choroidal neovascularization. "
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    • "Moreover, it interacts by cross-talking with VEGF to control tumor growth, metastasis and angiogenesis [15] [16] [17]. Due to its effects on angiogenesis process, α v β 3 integrin is one of the most promising targets for cancer therapy [10] and targeting drug delivery [18] [19]. For α v β 3 integrin targeting, cyclic pentapeptides, such as cyclic arginineglycine-asparagine-tyrosine-lysine (cRGDyk) and cyclic arginineglycine-asparagine-phenylalanine-lysine (cRGDfk) have been widely used, due to their high affinities and specificities, as well as their long half-lives. "
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    • "psoriasis, and consequently, the expression of specific subtypes of integrin receptors is regulated with respect to cell type, differentiation status and diseased state (Call-Culbreath and Zutter, 2008). The tissue-specific expression of specific integrin receptors can be exploited for the site-specific delivery of drugs (Dunehoo et al., 2006). An example is the human integrin ␣ 2 ␤ 1 receptor that belongs to the collagen-binding integrin subfamily , and it is the only collagen I integrin receptor expressed on keratinocytes in the basal layer of the skin (Parks, 2007). "
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