Y₁ receptor ligand-based nanomicelle as a novel nanoprobe for glioma-targeted imaging and therapy

Due to the molecular and cellular heterogeneity of glioma, discovery of novel targeted sites and ligands for glioma imaging and therapy remains challenging. Neuropeptide Y (NPY) Y₁ receptors (Y₁Rs) are highly over expressed in various brain tumors including glioma, and can serve as potential targeting sites for glioma imaging and therapy. Here, we show by in vivo fluorescent imaging that a highly selective Y₁R ligand, [Asn⁶, Pro³⁴] NPY (AP-NPY), facilitated circumvention of the blood brain barrier (BBB) by nanomicelles specifically targeting glioma. Modification with AP-NPY stabilized doxorubicin-loaded nanomicelles in the normal physiological state and promoted drug release in the acidic tumor microenvironment. Furthermore, targeted delivery of AP-NPY nanomicelles improved the therapeutic efficacy of doxorubicin for glioma, producing a prolonged survival rate. These results suggest that Y₁R is a novel targeted receptor, and its selective ligand AP-NPY improves BBB permeability and glioma targeting. Our study paves the way for developing a novel delivery system for diagnosis and treatment of glioma in which Y₁Rs are over expressed.