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A Novel Redox-Sensitive Drug Delivery System Based on Trimethyl-Locked Polycarbonate.
Dongdong Wang1, Mu Li1, Hanning Zhang1
1State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China.
Biomacromolecules
|August 16, 2023
Summary
Novel polymer nanocarriers respond to tumor microenvironments for targeted cancer therapy. These MTC-based micelles release drugs specifically when the NQO1 enzyme is present, improving treatment precision.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Stimuli-responsive polymer nanocarriers offer controlled drug release in cancer therapy.
- NAD(P)H: quinone oxidoreductase 1 (NQO1) is upregulated in tumors and can activate prodrugs.
- Targeting NQO1 offers a strategy for enzyme-mediated drug delivery.
Purpose of the Study:
- To synthesize a novel redox-sensitive monomer (MTC) for stimuli-responsive polymer nanocarriers.
- To develop MTC-based amphiphilic block copolymers and self-assemble them into micelles.
- To evaluate the drug delivery potential of these nanomicelles in an NQO1-mediated tumor microenvironment.
Main Methods:
- Synthesis of a novel redox-sensitive carbonate monomer (MTC).
- Preparation of amphiphilic block copolymers via ring-opening polymerization.
- Self-assembly of poly(ethylene glycol)-b-PMTC into micelles for doxorubicin (DOX) encapsulation.
- In vitro evaluation of redox-responsive drug release, biocompatibility, and hemocompatibility.
- Assessment of NQO1 enzyme-mediated drug release and cytotoxicity.
Main Results:
- Successfully synthesized MTC monomer and prepared poly(ethylene glycol)-b-PMTC block copolymers.
- Polymer micelles efficiently encapsulated doxorubicin (DOX) and exhibited redox-responsive drug release.
- In vitro studies confirmed excellent biocompatibility and hemocompatibility of the nanomicelles.
- Drug release was significantly reduced in NQO1-inhibited cells, demonstrating enzyme-specific release.
- Cytotoxicity was decreased in the presence of NQO1 enzyme inhibitors, indicating targeted drug delivery.
Conclusions:
- MTC-based polycarbonate micelles demonstrate efficient drug encapsulation and stimuli-responsive release.
- The nanomicelles show potential for targeted drug delivery in NQO1-overexpressed tumors.
- This platform offers a promising approach for intelligent nanocarriers in cancer therapy.
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