The Functions and Applications of RGD in Tumor Therapy and Tissue Engineering

Abstract

Arginine-Glycine-Aspartic (RGD), is the specific recognition site of integrins with theirs ligands, and regulates cell-cell and cell-extracellular matrix interactions. The RGD motif can be combined with integrins overexpressed on the tumor neovasculature and tumor cells with a certain affinity, becoming the new target for imaging agents, and drugs, and gene delivery for tumor treatment. Further, RGD as a biomimetic peptide can also promote cell adherence to the matrix, prevent cell apoptosis and accelerate new tissue regeneration. Functionalizing material surfaces with RGD can improve cell/biomaterial interactions, which facilitates the generation of tissue-engineered constructs. This paper reviews the main functions and advantages of RGD, describes the applications of RGD in imaging agents, drugs, gene delivery for tumor therapy, and highlights the role of RGD in promoting the development of tissue engineering (bone regeneration, cornea repair, artificial neovascularization) in recent years.

RGD-Functionalization of Poly(2-oxazoline)-Based Networks for Enhanced Adhesion to Cancer Cells

“…In this study, the concept was transferred to the functionalization of ground gel particles in suspension by thiol-ene reactions, benefiting from the fact that they are insensitive to water [39]. The cyclic pentapeptide, c(RGDfC), was chosen, because of its enhanced cancer cell recognition, due to the RGD motif geometrically constrained in the pentacycles bearing a bulky D-amino acid (D-phenylalanine in this case) [15,18,19] and the presence of the thiol-bearing L-cysteine for thiol-ene reactions. After UV-irradiating a mixture of the peptide and the freshly ground, FITC-functionalized hydrogel, the suspension was used for cell tests (see below).…”

“…BON cells were chosen, because of their pronounced surface expression of highly active α v β 5 -integrins, according to fluorescence-activated cell sorting measurements [42]. The α v β 5 -integrin, like its α v β 3 congener, has been reported to show an interaction of supreme strength with the RGD motif in peptide pentacycles [18,19]. In order to investigate the adherence of microparticles to these types of cells, the cells were seeded on glass cover slips and incubated with the hydrogel-containing media.…”

“…The mechanism of RGD motif recognition and subsequent cell attachment is based on the presence of integrins on cell surfaces. In particular, the α v β 5 -integrin and its α v β 3 congener have been reported to show strong interaction with the cyclic RGD motif [18,19]. Due to the known overexpression, as well as the high activity of integrins in tumor cells [20,21], research started to focus on the preparation of RGD-functionalized hydrogels for enhanced cancer imaging and for the development of targeted strategies for cancer treatment [9,22].…”

Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases

“…RGD peptides can be labeled with radioisotopes, near IR (NIR) dyes, and magnetic resonance imaging (MRI) contrast agents. As an example, cyclic RGDfK was linked to a fusion of human serum albumin and tissue inhibitor of metalloproteinase 2 (HSA-TIMP2) to make RGD-HSA-TIMP2 (Figure 3E) [59]. 68 Ga-NOTA- and 123 I-radiolabeled were incorporated to RGD-HSA-TIMP2 for cancer diagnostics that can be observed by positron emission tomography (PET) and single photon emission computed tomography (SPECT).…”

Concentric bioprinting of alginate-based tubular constructs using multi-nozzle extrusion-based technique

“…These methods usually use poly(ε-caprolactone) (PCL), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), polyglycolic acid (PGA) and poly(ethylene-co-vinyl acetate) (PEVA) to fabricate products; The product fabricated can reach a resolution of approximately 7 μm [15] . Although these methods have proven to be effective in creating tubular structures, these synthetic polymeric materials lack adhesion factors such as arginine-glycine-aspartic acid (RGD) which are important for cell adhesion, proliferation and matrix production [16,17] . Moreover, these materials usually degrade-although only after long periods of time-and would induce foreign body response by the host [18] which could be T lethal to the patient in the long run [19] .…”