Related Experiment Video
Updated: Jun 23, 2025
A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Disulfide bonds as a molecular switch of enzyme-activatable anticancer drug precise release for fluorescence imaging
Junwu Wei1, Yangyang Qian2, Lijun Bao1
1College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, PR China.
Abstract:
Enzyme-activatable drug delivery systems have been developed for cancer diagnosis and therapy. However, targeted intracellular drug delivery is a challenge for precisely tumor imaging and therapy due to the increased stability of copolymer nanoparticles (NPs) is accompanied by a notable decrease in enzyme degradation. Herein, disulfide bond was designed as an enzyme-activatable molecular switch of SS-P(G2)2/DOX NPs. The copolymer NPs consists of polyvinylpyrrolidone (PVP) with disulfide bonds in the center and enzyme-degradable peptide dendrites (Phe-Lys) to form dendritic-linear-dendritic triblock copolymers (TBCs). The amphiphilic TBCs could be split into two identical amphiphilic diblock copolymers (DBCs) by glutathione (GSH) in cancer cells specifically while maintaining the same hydrophilic-lipophilic equilibrium. This structural transformation significantly reduced the stability of copolymer NPs and enhanced sensitivity of DOX release by cathepsin B-activated. Subsequently, the released DOX acted as an indicator of fluorescence imaging and chemotherapy drug for cancer cells. The polymeric NPs achieved excellent drug-loaded stability and prolonged blood circulation in vivo, and realized fluorescence imaging and specific cancer cell killing capabilities by responding to the overexpression of GSH and cathepsin B in tumor cells. Furthermore, the copolymer NPs demonstrated excellent blood compatibility and biosafety. Therefore, a novel strategy based on one tumor marker acting as the switch for another tumor microenvironment responsive drug delivery system could be designed for tumor intracellular imaging and chemotherapy.
Insights
This study introduces enzyme-activatable copolymer nanoparticles (NPs) for cancer therapy. These nanoparticles release drugs in response to tumor markers, enabling precise imaging and chemotherapy with enhanced biosafety.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery Systems
Background:
- Enzyme-activatable drug delivery systems are crucial for cancer diagnosis and therapy.
- Targeted intracellular drug delivery faces challenges due to nanoparticle stability hindering enzyme degradation.
- Precisely controlling tumor imaging and therapy requires overcoming these delivery hurdles.
Purpose of the Study:
- To design enzyme-activatable copolymer nanoparticles (NPs) for targeted intracellular drug delivery in cancer therapy.
- To develop a system that responds to specific tumor microenvironment markers for enhanced drug release and imaging.
- To improve the efficacy and safety of cancer treatment through novel drug delivery strategies.
Main Methods:
- Synthesized dendritic-linear-dendritic triblock copolymers (TBCs) with disulfide bonds and peptide dendrites.
- Formulated SS-P(G2)2/DOX NPs, utilizing polyvinylpyrrolidone (PVP) and glutathione (GSH)-cleavable disulfide bonds.
- Investigated the structural transformation of TBCs into diblock copolymers (DBCs) triggered by glutathione (GSH) and cathepsin B activation for DOX release.
Main Results:
- The copolymer NPs demonstrated excellent drug-loaded stability and prolonged blood circulation in vivo.
- The NPs achieved specific cancer cell killing and fluorescence imaging capabilities by responding to overexpressed GSH and cathepsin B in tumor cells.
- The structural transformation significantly reduced NP stability, enhancing drug release sensitivity.
Conclusions:
- A novel strategy was developed using one tumor marker to activate another tumor microenvironment-responsive drug delivery system.
- The designed copolymer NPs offer a promising approach for tumor intracellular imaging and chemotherapy.
- The study highlights the potential of enzyme-activatable NPs for improved cancer treatment with excellent biocompatibility and biosafety.
More Related Videos
08:54Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies
Published on: February 17, 2023
09:37Combining Non-reducing SDS-PAGE Analysis and Chemical Crosslinking to Detect Multimeric Complexes Stabilized by Disulfide Linkages in Mammalian Cells in Culture
Published on: May 2, 2019