Cholera Toxin Subunit B Enabled Multifunctional Glioma‐Targeted Drug Delivery. Issue 23 (25th August 2017)

• Record Type: Journal Article
• Authors: Guan, Juan; Zhang, Zui; Hu, Xuefeng; Yang, Yang; Chai, Zhilan; Liu, Xiaoqin; Liu, Jican; Gao, Bo; Lu, Weiyue; Qian, Jun; Zhan, Changyou
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 23(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-08-25
• Subjects: blood–brain barrier -- cholera toxin subunit B -- glioma -- protein corona -- targeted drug delivery; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201700709
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Glioma is among the most formidable brain cancers due to location in the brain. Cholera toxin subunit B (CTB) is investigated to facilitate multifunctional glioma‐targeted drug delivery by targeting the glycosphingolipid GM1 expressed in the blood–brain barrier (BBB), neovasulature, and glioma cells. When modified on the surface of poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (CTB‐NPs), CTB fully retains its bioactivity after 24 h incubation in the fresh mouse plasma. The formed protein corona (PC) of CTB‐NP and plain PLGA nanoparticles (NP) after incubation in plasma is analyzed using liquid chromatography tandem massspectrometry (nano‐LC‐MS/MS). CTB modification does not alter the protein components of the formed PC, macrophage phagocytosis, or pharmacokinetic profiles. CTB‐NP can efficiently penetrate the in vitro BBB model and target glioma cells and human umbilical vascular endothelial cells. Paclitaxel is loaded in NP (NP/PTX) and CTB‐NP (CTB‐NP/PTX), and their antiglioma effects are assessed in nude mice bearing intracranial glioma. CTB‐NP/PTX can efficiently induce apoptosis of intracranial glioma cells and ablate neovasulature in vivo, resulting in significant prolongation of survival of nude mice bearing intracranial glioma (34 d) in comparison to those treated with NP/PTX (29 d), Taxol (24 d), and saline (21 d). The present study suggests a potential multifunctional glioma‐targeted drug delivery system enabled by cholera toxin subunit B. Abstract : Cholera toxin subunit B (CTB), the nontoxic moiety of cholera toxin, is able to circumvent the blood–brain barrier, and to target neovasculature and glioma cells. CTB modification on the surface of polymeric nanoparticles does not significantly alter components of the formed protein corona. CTB retains bioactivity during blood circulation, presenting a promising ligand for multifunctional targeting of glioma.