Targeting Integrins in Cancer Nanomedicine: Applications in Cancer Diagnosis and Therapy

Abstract

Due to advancements in nanotechnology, the application of nanosized materials (nanomaterials) in cancer diagnostics and therapeutics has become a leading area in cancer research. The decoration of nanomaterial surfaces with biological ligands is a major strategy for directing the actions of nanomaterials specifically to cancer cells. These ligands can bind to specific receptors on the cell surface and enable nanomaterials to actively target cancer cells. Integrins are one of the cell surface receptors that regulate the communication between cells and their microenvironment. Several integrins are overexpressed in many types of cancer cells and the tumor microvasculature and function in the mediation of various cellular events. Therefore, the surface modification of nanomaterials with integrin-specific ligands not only increases their binding affinity to cancer cells but also enhances the cellular uptake of nanomaterials through the intracellular trafficking of integrins. Moreover, the integrin-specific ligands themselves interfere with cancer migration and invasion by interacting with integrins, and this finding provides a novel direction for new treatment approaches in cancer nanomedicine. This article reviews the integrin-specific ligands that have been used in cancer nanomedicine and provides an overview of the recent progress in cancer diagnostics and therapeutic strategies involving the use of integrin-targeted nanomaterials.

Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy

“…In the last two decades, many smart nanoplatforms have been designed by introducing stimuli and targeting moieties into polymers of DDSs [93][94][95][96][97]. Some pH-and redox-responsive polymeric NPs are described here as the most commonly used triggers in DDSs.…”

“…This DDS exerts cancer targeting ability through the folate receptor (FR) interfering with endocytosis and pH-triggered drug release by the breaking of the hydrazine bond under acidic conditions (Figure 3). Xiong et alrecently reported on a multifunctional pH-responsive DDS composed of the diblock PEO-b-PCL copolymer and the αvβ3 integrin-targeting ligand, RGD4C, on the micellar surface [94,95]. The delivery systems are based on RGD4C-PEO-b-P (CL-Hyd-DOX) micelles, including the hydrophobic core (PCL), the drug DOX incorporated in the core via a pH-labile hydrazonebond, and a hydrophilic shell (PEO) decorated with the targeting peptide ligand RGD4C.…”

The Biological Functions and Clinical Applications of Integrins in Cancers

“…It is worth noting that new anti-cancer therapies targeting integrins using nanoparticles as carriers are emerging. The treatment strategy is to use integrin-specific ligands to engineer nanoparticles, thereby increasing their affinity for cancer cells (Wu P. H. et al, 2019). In summary, integrins have shown great potential in the diagnosis, prognosis, and treatment of cancer.…”

Solid phase synthesis in the development of magnetic resonance imaging probes

“…Strategies for targeting with either RGD or NGR have been widely exploited in diagnostics and therapeutics. [81][82][83][84][85][86][87] A lysine residue was also incorporated into the peptide sequence to enable simple coupling of pre-prepared tris-tBu-DOTA using standard coupling procedures. The inclusion of two binding motifs demonstrates the simple customisation available using such synthetic techniques.…”