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

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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.

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