Modulating angiogenesis with integrin-targeted nanomedicines

Abstract

Targeting angiogenesis-related pathologies, which include tumorigenesis and metastatic processes, has become an attractive strategy for the development of efficient guided nanomedicines. In this respect, integrins are cell-adhesion molecules involved in angiogenesis signaling pathways and are overexpressed in many angiogenic processes. Therefore, they represent specific biomarkers not only to monitor disease progression but also to rationally design targeted nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to specific integrins have been widely utilized to provide ligand-mediated targeting capabilities to small molecules, peptides, proteins, and antibodies, as well as to drug/imaging agent-containing nanomedicines, with the final aim of maximizing their therapeutic index. Within this review, we aim to cover recent and relevant examples of different integrin-assisted nanosystems including polymeric nanoconstructs, liposomes, and inorganic nanoparticles applied in drug/gene therapy as well as imaging and theranostics. We will also critically address the overall benefits of integrin-targeting.

Integrins as Therapeutic Targets: Successes and Cancers

“…Nevertheless, these data may yet enable novel strategies based on αvβ3. Moreover, despite conflicting preclinical data, many studies still therapeutically target endothelial αvβ3 (reviewed in [ 31 ]).…”

Recent Advances in Nanotheranostics for Treat‐to‐Target of Rheumatoid Arthritis

“…Integral proteins family is associated with the upregulation of angiogenesis 108. Previous researches found that α v β 3 ‐integrin antagonist could specifically induce the apoptosis of VECs, thereby inhibiting angiogenesis and alleviating arthritis severity 109.…”

“…[107] Integral proteins family is associated with the upregulation of angiogenesis. [108] Previous researches found that α v β 3integrin antagonist could specifically induce the apoptosis of VECs, thereby inhibiting angiogenesis and alleviating arthritis severity. [109] Zhou et al recently developed a nanocarrier system translatable lipase-labile (Sn 2) fumagillin prodrug (Fum-PD) to deliver Fum, which was anticipated to improve drug retention time in the circulation, enhancing net drug delivery to angiogenic endothelial cells via "contact-facilitated drug delivery."…”

Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein

“…Finally, the tumor-targeting precision of drugs [25,26], NPs [27,28], polymers [29], biomaterials [30], or nanostructured materials [20,31,32] can be strongly improved by conjugation with peptide ligands addressing integrin receptors overexpressed by cancer cells [20,33,34]. The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression, and metastatization of solid tumors, making them an appealing target for cancer therapy [35].…”