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Combination Glioma Therapy Mediated by a Dual‐Targeted Delivery System Constructed Using OMCN–PEG–Pep22/DOX
Author(s) -
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
Publication year - 2018
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201801905
Subject(s) - glioma , drug delivery , cancer research , photothermal therapy , materials science , chemistry , medicine , pharmacology , nanotechnology
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.