Development a hyaluronic acid ion-pairing liposomal nanoparticle for enhancing anti-glioma efficacy by modulating glioma microenvironment

Drug Delivery

Xu Song¹  Liuqing Yang¹  Tijia Chen¹  Ting Gong¹  Kejun Jiang¹  Zhirong Zhang¹  Tao Gong¹  Yingying Hou¹  Xun Sun¹ 

[1] Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR Chin;

关键词: Hyaluronic acid;    glioma;    TAMs;    CD44;    CSCs;   

DOI  :  10.1080/10717544.2018.1431979

来源: publisher

【 摘 要 】

Glioma, one of the most common brain tumors, remains a challenge worldwide. Due to the specific biological barriers such as blood–brain barrier (BBB), cancer stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then, these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which showed near-spherical morphology with an average size of 155.8 nm and uniform distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor, which is over-expressed on the surface of tumor cells, other associated cells (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma efficacy and mechanisms in vivo and in vitro. The strong anti-glioma efficacy could attribute to the accumulation in glioma site and the regulation of tumor microenvironment with depletion of TAMs, inhibition of VMs, and elimination of CSCs.

【 授权许可】

CC BY