Substance P Mediated DGLs Complexing with DACHPt for Targeting Therapy of Glioma

Abstract

Currently, glioblastoma (glioma) is described as the deadliest brain tumor for its invasive natural with exceeding difficulty in surgical excision. Blood-brain barrier (BBB) can restrict the penetration of most therapeutic reagents including platinum (Pt)-based drugs-the most widely used reagents in clinical trials for their revolutionized cancer chemotherapy against a broad range of tumors. Nanomedicine represents a promising strategy for the intravenous delivery of Pt-based drugs into the brain. In this research, with the aim of malignant glioma treatment by Pt-based drugs, a novel nano drug carrier was developed: dendrigraft poly-L-lysines (DGLs) was PEGylated, linked with diethylenetriaminpentaacetic acid (DTPA) to complex (1,2-diaminocyclohexane)platinum(II) (DACHPt), and modified with Substance P (SP) as a BBB/glioma dual-targeting moiety. The preparation and characterization of the platform were exhibited in detail. The increased targeting capability and antitumor effect was found both in vitro and in vivo. The well-defined chemical composition, rigorously nanoscaled size and the first attempt of using SP as a BBB/glioma dual-targeting group were highlighted. The combined results suggest this strategy may serve as novel formulation for Pt-based drugs with the aim of clinical glioma treatment.

Keywords: Substance P; blood-brain barrier; drug delivery; glioma; platinum drug.