Development of a hybrid nanocarrier-recognizing tumor vasculature and penetrating the BBB for glioblastoma multi-targeting therapy. Issue 23 (5th June 2019)

• Record Type: Journal Article
• Authors: Fan, Rangrang; Chuan, Di; Hou, Huan; Chen, Haifeng; Han, Bo; Zhang, Xiaoning; Zhou, Liangxue; Tong, Aiping; Xu, Jianguo; Guo, Gang
• Is Part Of: Nanoscale. Volume 11:Issue 23(2019)
• Page Start: 11285
• Page End: 11304
• Publication Date: 2019-06-05
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/c9nr01320b
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : The multi-targeting hybrid nanocarriers have been developed as excellent anticancer drug delivery system with enhanced BBB transporting, glioma targeting and tumor penetrating effect. Abstract : The success of glioma chemotherapy is hampered by poor drug penetration ability across the blood–brain barrier (BBB) and low intratumoral drug concentration. Novel tumor-targeted delivery systems are useful in specifically accumulating in the tumor foci and penetrating into the glioma core after entering into the brain. Here we show that a multi-targeting hybrid nanocarrier (Pep-MLHA HNPs) system based on hyaluronic acid (HA)-modified polymer and a functional peptide possesses multi-target capability and stronger penetration ability into the core of three-dimensional tumor spheroids, could migrate efficiently across the BBB in vitro . The intensity of the Pep-MLHA HNPs after transporting across the BBB was 5.2-fold and 5.6-fold higher than that of ML NPs in C6 and U87 cells, respectively. More interestingly, this multi-targeting hybrid system displayed high colloidal stability in PBS solution, and weak negative zeta potential (−1.99 ± 0.655 mV) minimizing nonspecific interactions with plasma proteins and promoting long-term circulation in vivo . Additionally, the multi-targeting hybrid system induced enhanced tumor localization in U87 in situ -bearing nude mice and xenograft-bearing nude mice after systemic administration. Furthermore, docetaxel (DTX)-loaded Pep-MLHA HNPs showed negligible systemic toxicity and enhanced therapeutic efficacy, with significantly improved survival rates in intracranial C6 glioma-bearing rats. The 50% survival rate of DTX/Pep-MLHA HNPs-treated rats (40 days) was significantly longer than that of rats treated with NS (22 days), Taxotere® (25 days), DTX/ML NPs (25 days), DTX/Pep NPs (32 days) and DTX/MLHA NPs (29 days). All the results suggested that the multi-targeting hybrid nanocarrier system is promising for glioma treatment.