Tumor-Associated Fibronectin Targeted Liposomal Nanoplatform for Cyclophilin A siRNA Delivery and Targeted Malignant Glioblastoma Therapy

Frontiers in Pharmacology

Yingjie Xu¹  Lei Zhang²  Yan Nie⁴  Ao Zhang⁴  Xiaoding Xu⁴  Phei Er Saw⁴ 

[1] Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;

关键词: nanoparticle;    aptide;    siRNA;    targeted delivery;    glioblastoma;   

DOI  :  10.3389/fphar.2018.01194

来源: DOAJ

【 摘 要 】

Malignant glioblastoma (GBM) is the most aggressive brain cancer that has a very low survival rate. With the rapid development of nanotechnology in the past few decades, the use of nanoparticles (NPs) for nucleic acid delivery is expected to have a revolutionary impact on GBM therapy. However, clinical success in GBM therapy remains a formidable challenge, mainly due to suboptimal in vivo delivery of therapeutics to glioma cells. Herein, we developed an aptamer-like peptide (aptide)-decorated liposomal nanoplatform for systemic small interfering RNA (siRNA) delivery and targeted GBM therapy. This nanoplatform is mainly composed of the following key components: (i) classic liposome structure with an aqueous core that can encapsulate therapeutic siRNA; (ii) hydrophilic polyethylene glycol (PEG) chains on the outer shell to prolong blood circulation; and (iii) surface-encoded aptide to specifically target the extra-domain B (EDB) of fibronectin that over-expressed on glioma cells. After systemic administration of these new siRNA delivery NPs, they can target the glioma cells and efficiently inhibit the GBM tumor growth by silencing the expression of cyclophilin A (CypA), which is up-regulated in brain cancer and plays an important role in malignant transformation of brain cancer and maintaining glioma cell stemness. These results suggest that the reported RNA interference (RNAi) NP platform herein could become an effective tool for targeted GBM therapy.

【 授权许可】

Unknown