Dual-modified natural high density lipoprotein particles for systemic glioma-targeting drug delivery

Lin Cui,Yuli Wang,Meng Liang,Xiaoyang Chu,Shiyao Fu,Chunsheng Gao,Qianqian Liu,Wei Gong,Meiyan Yang,Zhiping Li,Lian Yu,Chunrong Yang,Zhide Su,Xiangyang Xie,Yang Yang

doi:10.1080/10717544.2018.1519002

Lin Cui, Yuli Wang + Show 13 more

Open Access

https://doi.org/10.1080/10717544.2018.1519002

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Journal: Drug Delivery	Publication Date: Jan 1, 2018
Citations: 24	License type: open-access

Affiliation: Jiamusi University, Weifang People's Hospital

Abstract

Therapeutic outcome for the treatment of glioma was often limited due to the two barriers involved: the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Therefore, the development of nanocarriers that possess both BBB and BBTB permeability and glioma-targeting ability is of great importance for the chemotherapy of glioma. New frontiers in nanomedicine are advancing the research of new biomaterials. Here we constructed a natural high-density lipoprotein particle (HDL)-based drug delivery system with the dual-modification of T7 and dA7R peptide ligand (T7/dA7R-HDL) to achieve the above goals. HDL, the smallest lipoprotein, plays a biological role and is highly suitable as a platform for delivering imaging and therapeutic agents. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. dA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. 10-Hydroxycamptothecin (HCPT), a hydrophobic anti-cancer drug, was used as the model drug in this study. By combining the dual-targeting delivery effect, the dual-modified HDL displayed higher glioma localization than that of single ligand-modified HDL or free HCPT. After loading with HCPT, T7/dA7R-HDL showed the most favorable anti-glioma effect in vivo. These results demonstrated that the dual-targeting natural nanocarriers strategy provides a potential method for improving brain drug delivery and anti-glioma treatment efficacy.

Highlights

Glioma is considered as one of the most aggressive and lethal types of cancers
(C), the extracted high-density lipoprotein particle (HDL) in our team demonstrated similar infrared and circular dichroism (CD) spectrum as the reference HDL. These results suggested that the method adopted in this study was suitable for the isolation of HDL from human blood
The present results suggested that HDL with T7 and dA7R modification possessed the penetrating ability to the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB)

Summary

Introduction

Glioma is considered as one of the most aggressive and lethal types of cancers. Despite the great advances in surgery, the glioma patients still have an extremely poor prognosis and a high risk of recurrence due to the highly infiltrative and invasive nature of glioma cells (Donahue et al, 2008). Chemotherapy is indispensable for subsequent treatment after surgery resection of glioma. Chemotherapy is often dramatically hindered by the special pathological and physiological characteristics of giloma (Shaw et al, 2017). The blood-brain barrier (BBB) is considered as a major barrier that restricts the distribution of drugs from blood to brain, resulting in glioma recurrence. The non-targeted nature of drugs relates to the severe side effects and recurrence of glioma. The median prognosis for patients with glioma is approximately 15 months (Dolecek et al, 2012)

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