Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental breast cancer metastasis in the brain

Abstract

Metastasis is the main killer in cancer; consequently, there is great interest in novel approaches to prevent and treat metastatic disease. Brain metastases are particularly deadly, as the protection of the blood-brain barrier obstructs the passage of common anticancer drugs. This study used magnetic resonance imaging (MRI) to investigate the therapeutic effects of nanoparticles coated with a tumor-penetrating peptide (iRGD) against a preclinical model of breast cancer brain metastasis. Single doses of iRGD nanoparticle were administered intravenously, and the effect on tumor growth was observed over time. iRGD nanoparticles, when applied in the early stages of metastasis development, strongly inhibited tumor progression. Overall, this study demonstrated for the first time that a single dose of iRGD nanoparticle can have a significant effect on metastatic tumor progression and nonproliferative cancer cell retention when applied early in course of tumor development. These data suggest that iRGD nanoparticles may be useful in preventatively reducing metastasis after a cancer diagnosis has been established.

Tumor penetrating peptides for improved drug delivery

“…One possibility is to couple the peptide onto the surface of long-circulating nanoparticles or incorporate it into a dendrimer. Nanoparticle-coupled iRGD is more effective in inhibiting metastasis than an equivalent amount of free iRGD peptide [57]. The half-life may be less of a problem in human patients than in mouse experiments, because the logistics of prolonged infusion or multiple injections are much easier.…”

“…An inherent functional activity of a tumor-homing peptide can also be enhanced by NP presentation. The anti-metastatic activity of the iRGD peptide [70] is stronger when the peptide is on NPs than when it is used as soluble peptide [57]. …”

The Diagnostic Value of miR-155 Expression in the Serum of Patients with Breast Cancer According to Molecular Subtypes of Breast Cancer

“…Breast cancer (BC) is the most prevalent cancer in women comprising about 16% of all cancer cases in women (1,2). A subtype of BC, called triple negative, without ER/PR/Her2 expression grows without the need for external growth hormones (3), which makes tumors grow quickly, Luminal A: ER and/or PR positive and HER2-negative and Luminal B: ER and/or PR and HER2 positive (4).…”

A Comprehensive Evaluation of the Activity and Selectivity Profile of Ligands for RGD-binding Integrins

“…Indeed, integrin antagonists were shown to have high therapeutic potential1314151617. Specifically, selective integrin ligands were widely used to target integrin-overexpressing tumors, as inhibitors of cancer angiogenesis1819 and as blockers of excessive blood coagulation15. Modified integrin ligands were also used for carrying radionuclei or dyes for tumor diagnosis (using PET, SPECT or fluorescent probes)20, or for functionalization of adhesive surfaces and development of cell instructive biomaterials21222324.…”