Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 40, Pages 34603-34617Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b05997
Keywords
glioma; drug delivery; platinum drug; blood-brain barrier; Substance P
Funding
- National Natural Science Funds of China [21602030, 81172993]
- National Basic Research Program of China (973 Program) [2013CB932500]
- Shanghai Sailing Program [16YF1400900]
- Scientific Research Foundation of Fudan University [JJF301103]
- National Science Fund for Distinguished Young Scholars [81425023]
- Shanghai Municipal Commission of Health and Family Planning [201410017]
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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-Llysines (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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