title: Smart nanodevice combined tumor-specific vector with cellular microenvironment-triggered property for highly effective antiglioma therapy.
abstract: Malignant glioma, a highly aggressive tumor, is one of the deadliest types of cancer associated with dismal outcome despite optimal chemotherapeutic regimens. One explanation for this is the failure of most chemotherapeutics to accumulate in the tumors, additionally causing serious side effects in periphery. To solve these problems, we sought to develop a smart therapeutic nanodevice with cooperative dual characteristics of high tumor-targeting ability and selectively controlling drug deposition in tumor cells. This nanodevice was fabricated with a cross-linker, containing disulfide linkage to form an inner cellular microenvironment-responsive "-S-S-" barrier, which could shield the entrapped drug leaking in blood circulation. In addition, dehydroascorbic acid (DHA), a novel small molecular tumor-specific vector, was decorated on the nanodevice for tumor-specific recognition via GLUT1, a glucose transporter highly expressed on tumor cells. The drug-loaded nanodevice was supposed to maintain high integrity in the bloodstream and increasingly to specifically bind with tumor cells through the association of DHA with GLUT1. Once within the tumor cells, the drug release was triggered by a high level of intracellular glutathione. When these two features were combined, the smart nanodevice could markedly improve the drug tumor-targeting delivery efficiency, meanwhile decreasing systemic toxicity. Herein, this smart nanodevice showed promising potential as a powerful platform for highly effective antiglioma treatment.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, ‡Department of Pharmaceutics, School of Pharmacy, and §Department of Medical Chemistry, School of Pharmacy, Fudan University , Shanghai 201203, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Shao
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.forename: Shixian
authors.initials: S
authors.lastname: Huang
authors.forename: Sumei
authors.initials: S
authors.lastname: Ren
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Kuang
authors.forename: Yubo
authors.initials: Y
authors.lastname: Guo
authors.forename: Haojun
authors.initials: H
authors.lastname: Ma
authors.forename: Sai
authors.initials: S
authors.lastname: An
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D004337:Drug Carriers; D005910:Glioma / Q000628:therapy*; D064593:Heterografts; D006801:Humans; D051379:Mice; D049329:Nanostructures; D059016:Tumor Microenvironment
chemical_list: D004337:Drug Carriers