title: T7 Peptide-Functionalized PEG-PLGA Micelles Loaded with Carmustine for Targeting Therapy of Glioma.
abstract: Glioma is regarded as the deadliest and most common brain tumor because of the extremely difficult surgical excision ascribed from its invasive nature. In addition, the natural blood-brain barrier (BBB) greatly restricts the therapeutics' penetration into the central nervous system. Carmustine (BCNU) is a widely used antiglioma drug in clinical applications. However, its serious complications prevent it from being applied in a clinical setting to some extent. Thus, it is urgent to explore novel BCNU delivery systems specially designed for glioma. Development of polymeric nanoparticles offers a favorable alternative to serve this purpose. Particularly, use of poly(lactic-co-glycolic acid) (PLGA) has been shown to be advantageous for its favorable biodegradability and biocompatibility, which ensure safe therapies. In this study, T7 peptide-conjugated, BCNU-loaded micelles were constructed successfully via the emulsion-solvent evaporation method. The micelles were characterized by transmission electron microscopy and dynamic light scattering in detail, and the capacity of BBB crossing was studied. The in vivo detecting results of the targeting effect using the BODIPY probe evidenced that T7-modified micelles showed a more pronounced accumulation and accumulated in the tumor more efficiently than in the unconjugated probe. Meanwhile, the targeting group exhibited the best curative effect accompanied with the lowest loss in body weight, the smallest tumor size, and an obviously prolonged survival time among the groups. In the near future, we believe the targeted delivery system specially designed for BCNU is expected to provide sufficient evidence to proceed to clinical trials.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang 150001, P.R. China.|Department of Neurosurgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine , Shanghai 201620, P.R. China.
authors.forename: Yunke
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Qinjun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Sai
authors.initials: S
authors.lastname: An
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Ruan
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Yinhao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine , Shanghai 201620, P.R. China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Lou
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
keywords: BCNU; blood-brain barrier; glioma; micelle; receptor-mediated endocytosis; transferrin receptor