Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy

• Published in: Biochemical and biophysical research communications Vol. 551; pp. 14 - 20
• Main Authors: Xu, Hengwu, Li, Chaoqun, Wei, Yinghui, Zheng, Hangsheng, Zheng, Hongyue, Wang, Binhui, Piao, Ji-Gang, Li, Fanzhu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-04-2021
• Subjects: Angiopep-2; Arsenic trioxide; Blood-brain barrier; Calcium arsenite liposome; Dual targeting; Glioma; Angiopep-2; Arsenic trioxide; Calcium arsenite liposome; Glioma; Blood-brain barrier; Dual targeting
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.02.138

The blood-brain barrier (BBB) is the most critical obstacle in the treatment of central nervous system disorders, such as glioma, the most typical type of brain tumor. To overcome the BBB and enhance drug-penetration abilities, we used angiopep-2-modified liposomes to deliver arsenic trioxide (ATO) across the BBB, targeting the glioma. Angiopep-2-modified calcium arsenite-loaded liposomes (A2–PEG–LP@CaAs), with uniformly distributed hydrodynamic diameter (96.75 ± 0.57 nm), were prepared using the acetate gradient method with high drug-loading capacity (7.13 ± 0.72%) and entrapment efficiency (54.30 ± 9.81%). In the acid tumor microenvironment, arsenic was responsively released, thereby exerting an anti-glioma effect. The anti-glioma effect of A2–PEG–LP@CaAs was investigated both in vitro and in vivo. As a result, A2–PEG–LP@CaAs exhibited a potent, targeted anti-glioma effect mediated by the lipoprotein receptor-related (LRP) receptor, which is overexpressed in both the BBB and glioma. Therefore, A2–PEG–LP@CaAs could dramatically promote the anti-glioma effect of ATO, as a promising strategy for glioma therapy.
Angiopep-2-modified calcium arsenite liposome (A2–PEG–LP@CaAs) was developed to improve BBB penetration efficiency, and achieve targeted and pH-responsive drug delivery against gliomas, providing novel insight into glioma therapy. [Display omitted]
•LP@CaAs can dramatically increase the entrapment of ATO.•Angiopep-2 can both transport across the BBB and target glioma cells.•A2–PEG–LP@CaAs could effectively improve anti-glioma efficacy.