Peptide-functionalized NaGdF₄ nanoparticles for tumor-targeted magnetic resonance imaging and effective therapy

Metallic nanoparticles showed potent efficacy for diagnosis and therapy of cancer, but their clinical applications are limited by their poor tumor-targeting ability. Herein, peptide-functionalized 9 nm NaGdF₄ nanoparticles (termed as, NaGdF₄@bp-peptide NPs) have been synthesized through the Gd-phosphate coordination reaction of the spherical NaGdF₄ nanoparticles with phosphopeptides (sequence: KLAKLAKKLAKLAKG(p-S)GAKRGARSTA, p-S means phosphorylated serine) including a p32 protein binding motif incorporating a cell-penetrating function, and a proapoptotic domain. The NaGdF₄@bp-peptide NPs are ready to be efficiently internalized by cancer cells; they show a much higher cytotoxicity in MCF-7 breast cancer cells than the casein phosphopeptide (CPP) modified NaGdF₄ nanoparticles (termed as, NaGdF₄@CPP NPs). Using mouse-bearing MCF-7 breast cancer as a model system, the in vivo experimental results demonstrate that NaGdF₄@bp-peptide NPs have integration of T₁-weighted magnetic resonance imaging (MRI) contrast and tumor-targeting functionalities, and are able to suppress tumor growth without causing systemic toxicity.