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Visible Light and Glutathione Dually Responsive Delivery of a Polymer-Conjugated Temozolomide Intermediate for Glioblastoma Chemotherapy
- Source :
- ACS Applied Materials & Interfaces. 13:55851-55861
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- Temozolomide (TMZ) is a prodrug of 5-(3-methyltriazene-1-yl)imidazole-4-carboxamide (MTIC, short-lived) and used as a first-line therapy drug for glioblastoma multiforme (GBM). However, little progress has been made in regulating the kinetics of TMZ to MTIC degradation to improve the therapeutic effect, particularly in the case of TMZ-resistant GBM. In this work, we introduced a strategy to cage MTIC by N-acylation of the triazene moiety to boost the MTIC stability, designed a diblock copolymer-based MTIC prodrug installed with a disulfide linkage, and achieved self-assembled polymer micelles without the concern of MTIC leakage under physiological conditions. Polymer micelles could be induced to disassemble by stimuli factors such as glutathione (GSH) and visible light irradiation through thiol/sulfide exchange and homolytic sulfide scission mechanisms, which contributed to MTIC release in GSH-dependent and GSH-independent pathways. The in vitro results demonstrated that microenvironment-responsive polymeric micelles benefited the suppression of both TMZ-sensitive and TMZ-resistant GBM cells. The chemistry of polymer-MTIC prodrug provided a new option for TMZ-based glioma treatment.
- Subjects :
- Materials science
Light
Cell Survival
Polymers
Surface Properties
Conjugated system
Micelle
chemistry.chemical_compound
Drug Delivery Systems
Cell Line, Tumor
Glioma
Temozolomide
medicine
Humans
Prodrugs
General Materials Science
Particle Size
Triazene
Antineoplastic Agents, Alkylating
Cell Proliferation
chemistry.chemical_classification
Molecular Structure
Glutathione
Prodrug
medicine.disease
Drug Liberation
chemistry
Cancer research
Thiol
Drug Screening Assays, Antitumor
Glioblastoma
medicine.drug
Subjects
Details
- ISSN :
- 19448252 and 19448244
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- ACS Applied Materials & Interfaces
- Accession number :
- edsair.doi.dedup.....3f0a8d4cc7b09335803db37bd4ccdc23