Recent Progress of RGD Modified Liposomes as Multistage Rocket Against Cancer

Abstract

Cancer is a life-threatening disease, contributing approximately 9.4 million deaths worldwide. To address this challenge, scientific researchers have investigated molecules that could act as speed-breakers for cancer. As an abiotic drug delivery system, liposomes can hold both hydrophilic and lipophilic drugs, which promote a controlled release, accumulate in the tumor microenvironment, and achieve elongated half-life with an enhanced safety profile. To further improve the safety and impair the off-target effect, the surface of liposomes could be modified in a way that is easily identified by cancer cells, promotes uptake, and facilitates angiogenesis. Integrins are overexpressed on cancer cells, which upon activation promote downstream cell signaling and eventually activate specific pathways, promoting cell growth, proliferation, and migration. RGD peptides are easily recognized by integrin over expressed cells. Just like a multistage rocket, ligand anchored liposomes can be selectively recognized by target cells, accumulate at the specific site, and finally, release the drug in a specific and desired way. This review highlights the role of integrin in cancer development, so gain more insights into the phenomenon of tumor initiation and survival. Since RGD is recognized by the integrin family, the fate of RGD has been demonstrated after its binding with the acceptor’s family. The role of RGD based liposomes in targeting various cancer cells is also highlighted in the paper.

Quantum Dot-Based Screening Identifies F3 Peptide and Reveals Cell Surface Nucleolin as a Therapeutic Target for Rhabdomyosarcoma

“…We included peptides specific for surface receptors known to be expressed on RMS cells (NCAM-1, EGFR, CB1, TFR1, and uPAR; see Supplementary Table S2 for an overview of the literature), or reported to successfully target other tumors, tumor blood vessels, or tumor lymphatic vessels (Nucleolin, CD13, p32). We also included integrin α v β 3 -targeting peptides (CRGDS, cRGDyK) since integrin α v β 3 is one of the most investigated targets [ 21 , 22 ] and we previously showed successful RMS-targeting with RGD-based peptides [ 23 , 24 ] ( Table 1 ). Expression of the targeted receptor was additionally verified by analysis of publicly available expression data ( Supplementary Figures S1–S3 ).…”

Profiling target engagement and cellular uptake of cRGD-decorated clinical-stage core-crosslinked polymeric micelles

“…Cyclic RGD is among the most widely studied targeting ligand and it has demonstrated strong affinities for α v β 3 integrin, a key receptor expressed by multiple cell populations including among others, cancer cells of the skin and of the breast, endothelial cells, and neutrophils. Surface functionalization of nanoparticles with targeting ligands such as cRGD has shown significant advantages in preclinical cancer nanotherapy studies [51,52].…”

Profiling target engagement and cellular uptake of cRGD-decorated clinical-stage core-crosslinked polymeric micelles

“…Cyclic RGD is among the most widely studied targeting ligand and it has demonstrated strong a nities for α v β 3 integrin, a key receptor expressed by multiple cell populations including among others, cancer cells of the skin and of the breast, endothelial cells and neutrophils. Surface functionalization of nanoparticles with targeting ligands such as cRGD has shown signi cant advantages in preclinical cancer nanotherapy studies [49,50]. However, in-depth cellular examination already revealed that RGDtargeting induced nanoparticle association with tumor vasculature while marginally reaching the tumor interstitium [29,51].…”