The blood-brain barrier and the blood-brain tumor barrier (BBTB) prevent most drugs entering brain tumors. Complicated preparation procedures of drug delivery systems and damage to normal brain tissue have limited the application of many strategies for the treatment of brain tumor in clinical trials. We have designed a bradykinin analog, retro-inverso bradykinin (RI-BK), which is characterized by resistance to proteolysis and high binding activity with the bradykinin type 2 (B-2) receptor. After systemic administration, RI-BK binds to B2 receptors and induces a change in zonula occluden-1 and depolymerization of F-actin to selectively open the BBTB. RI-BK increased the accumulation of drug-loaded nanocarriers in the glioma but not in normal brain. Co-administration with RI-BK enhanced the therapeutic efficiency of drug-loaded nanocarriers for glioma. These findings suggest that RI-BK could be translated into the clinic as an adjunctive treatment for malignant brain tumors. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
[1]Fudan Univ, Sch Pharm, Dept Pharmaceut, Key Lab Smart Drug Delivery,Minist Educ, Shanghai 201203, Peoples R China;
[2]Fudan Univ, Eye & ENT Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai 200030, Peoples R China
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