Combination Glioma Therapy Mediated by a Dual‐Targeted Delivery System Constructed Using OMCN–PEG–Pep22/DOX. Issue 42 (14th September 2018)

• Record Type: Journal Article
• Authors: Qian, Wenbo; Qian, Min; Wang, Yi; Huang, Jianfei; Chen, Jian; Ni, Lanchun; Huang, Qingfeng; Liu, Qianqian; Gong, Peipei; Hou, Shiqiang; Zhu, Hui; Jia, Zhongzheng; Shen, Dandan; Zhu, Changlai; Jiang, Rui; Sun, Junlong; Yao, Junzhong; Tang, Zhongyu; Ji, Xiang; Shi, Jinlong; Huang, Rongqin; Shi, Wei
• Is Part Of: Small. Volume 14:Issue 42(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-14
• Subjects: dual targeting -- glioma treatment -- LDLR -- nanoparticle design -- thermal therapy; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201801905
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Accumulating studies have investigated the efficacy of receptor‐mediated delivery of hydrophobic drugs in glioma chemotherapy. Here, a delivery vehicle comprising polyethylene glycol (PEG) and oxidized nanocrystalline mesoporous carbon particles (OMCN) linked to the Pep22 polypeptide targeting the low‐density lipoprotein receptor (LDLR) is designed to generate a novel drug‐loaded system, designated as OMCN–PEG–Pep22/DOX (OPPD). This system effectively targets glioma cells and the blood–brain barrier and exerts therapeutic efficacy through both near‐infrared (NIR) photothermal and chemotherapeutic effects of loaded doxycycline (DOX). Pathological tissue microarrays show an association of LDLR overexpression in human glioma tissue with patient survival.NIR irradiation treatment and magnetic resonance imaging results show that OPPD reaches the effective glioma‐killing temperature in a glioma‐bearing rat with a skull bone removal model and considerably reduces glioma sizes relative to the drug‐loaded system without the Pep22 peptide modification and the control respectively. Thus, OPPD not only effectively targets LDLR‐overexpressing glioma but also exerts a dual therapeutic effect by transporting DOX into the glioma and generating thermal effects with near‐infrared irradiation to kill tumor cells. These collective findings support the utility of the novel OPPD drug‐loaded system as a promising drug delivery vehicle for clinical application in glioma therapy. Abstract : A novel drug‐loaded system, OPPD, which uses PEG and OMCN linked to the Pep22 polypeptide targeting the LDLR, can effectively cross the BBB and target glioma cells exerting an outstanding therapeutic efficacy via the near‐infrared photothermal and chemotherapeutic effects of loaded DOX. The collective findings support the utility of OPPD, a promising drug‐delivery vehicle, for future clinical application in glioma therapy.