Integrin-Mediated Drug Delivery in Cancer and Cardiovascular Diseases with Peptide-Functionalized Nanoparticles

Abstract

In recent years progress has been speeding in studies of cell-cell interaction governed by adhesion molecules, and in particular by integrins and their ligands in cells and in the extracellular matrix. Integrins are distributed in a variety of tissues and blood cells. An increased expression of integrins and of their adhesion counterparts is often observed in sites relevant to disease states. Important roles are played by integrin α(v)β(3) in cancer angiogenesis and metastatic diffusion, in angiogenesis in ischemic tissues, in atherosclerotic damage and restenosis, and in osteoporosis; by integrin α(5)β(1) in angiogenesis processes; by integrin α(II)bβ(3), mediating adhesion of platelets to fibrinogen, in thrombotic conditions; by integrins α(4)β(1) and α(L)β(2) in inflammatory conditions, particularly autoimmune diseases and asthma. Therefore, medicinal chemists became attracted and engaged in research on integrins as therapeutic and diagnostic targets. Many efforts have been directed towards the development of molecular constructs including integrin ligands that can provide advanced tools for drug delivery, for imaging, or for their combination (theranostics), particularly by exploiting the new possibilities offered by nanoparticles. Here we will review the current status and the future perspective of integrin targeting of several kind of nanoparticles, going from most studied micelles, liposomes, polymeric nanoparticles to finish with inorganic nanoparticles of more recent employment. Perfluoroalkane filled microbubbles, although over the nanometric size (1-10 μm) will be shortly considered.

RNA interference targeting human integrin α6 suppresses the metastasis potential of hepatocellular carcinoma cells

“…This study showed that over-expression of integrin α6 in HCC is a strong indicator for more aggressive tumors and poorer clinical outcome. All the currently available therapies for HCC are mainly oriented towards removing or destroying the tumors, whereas few therapies aim at blocking the process of HCC metastasis [24]. This study would help us to understand the metastatic process of HCC better and develop targeted molecular therapy to improve patients’ survival.…”

Magnetic Nanoparticles in Cancer Theranostics

“…In recent years, many efforts have been focused to develop integrin ligands to target integrin receptors in pathological states. 92 Peptide ligands can also be used for cancer diagnosis. For example, chlorotoxin, a peptide with a high selectivity for membrane-bound matrix metalloproteinase-2 (MMP-2), is over expressed in various cancers such as glioma, prostate and intestinal cancer.…”

Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations

“…Integrins are key regulators of communication between cells and their microenvironment. They are directly involved in the interplay between pro-angiogenic growth factors and their receptors, thereby exercising varied biological functions such as cell adhesion, migration/invasion, proliferation, survival, and apoptosis [ 11 , 97 ]. Integrins are a set of heterodimeric transmembrane glycoproteins made up of different α and β subunits, and αvβ3-Integrin has received much attention as a potential anti-angiogenic target because it is upregulated in tumor-associated blood vessels [ 11 ].…”