Journal
ACS NANO
Volume 8, Issue 2, Pages 1191-1203Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn406285x
Keywords
polymeric micelles; dehydroascorbic acid; GLUT1; cellular microenvironment; antiglioma; glutathione triggered; U87 xenograft model
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Funding
- National Basic Research Program of China (973 Program) [2013CB932500]
- National Natural Science Foundation of China [81373355]
- Key new drug creation program [2009ZX09310-006]
- Program for New Century Excellent Talents in University
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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.
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