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Published on: June 13, 2014
Multifunctional Smart Injectable Triblock Copolymer Hydrogel for Highly Efficient Dual Drug-Gene Delivery in
Rishik Patra1, Satyajit Halder2,3, Rima Saha1
1Gene Therapy and Tissue Engineering Lab, Department of Polymer Science and Technology, University of Calcutta, 92, A.P.C. Road, Kolkata 700009, India.
Abstract:
Triple-negative breast cancer (TNBC) remains one of the most aggressive breast cancer subtypes, lacking targeted therapies and exhibiting elevated levels of intracellular Cu2+ ions. Smart multifunctional nanocarriers capable of dual drug-gene delivery offer a promising strategy for improved TNBC management. In this study, we present an injectable, triple-stimuli-responsive polymeric nanocarrier engineered via reversible addition-fragmentation chain-transfer (RAFT) polymerization for targeted TNBC theranostics. The amphiphilic triblock copolymer integrates three functional components: a photochromic spiropyran (SP) unit enabling light responsiveness, a pH-sensitive cationic hydroxyethyl methacrylate-glycine (HEMA-Gly) segment facilitating nucleic acid complexation, and a temperature-responsive N-isopropylacrylamide (NIPAAM) unit enabling thermally triggered behavior. Notably, the nanocarrier shows strong fluorescence quenching in the presence of Cu2+ ionsoverexpressed in TNBCsupporting selective cellular recognition. Doxorubicin (DOX) loading and release studies demonstrated controlled, sustained release under mildly acidic conditions mimicking the tumor microenvironment. In vitro evaluations using MDA-MB-231 TNBC cells confirmed the platform's multifunctionality. Cytotoxicity assays indicated biocompatibility, while fluorescence imaging revealed efficient cellular uptake of DOX-loaded micelles. Furthermore, the system modulated cell cycle progression and significantly enhanced intracellular and mitochondrial reactive oxygen species (ROS) production, indicating the potential to induce ROS-mediated apoptosis. Gene delivery experiments showed high transfection efficiency of nucleic acid-loaded micelles, attributed to the cationic HEMA-Gly block. Additionally, intracellular quenching studies confirmed the polymer's selective sensitivity toward TNBC-associated Cu2+ ions. Overall, the RAFT-synthesized triblock copolymer represents a versatile theranostic platform capable of simultaneous drug release, gene transfection, ROS induction, and Cu2+-guided TNBC detection. Its targeted responsiveness and multifunctional performance highlight its promise for advanced TNBC diagnostics and combination therapy.
Insights
Researchers developed a smart nanocarrier for triple-negative breast cancer (TNBC) that delivers drugs and genes. This advanced system targets cancer cells using copper ions and responds to light, pH, and temperature for enhanced theranostics.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Polymer Chemistry
Background:
- Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies.
- Elevated intracellular Cu2+ ions are characteristic of TNBC.
- Multifunctional nanocarriers offer a promising strategy for TNBC theranostics.
Purpose of the Study:
- To engineer an injectable, triple-stimuli-responsive polymeric nanocarrier for TNBC theranostics.
- To integrate light, pH, and temperature responsiveness with Cu2+ ion sensitivity.
- To achieve dual drug-gene delivery and enable Cu2+-guided detection.
Main Methods:
- Reversible addition-fragmentation chain-transfer (RAFT) polymerization was used to synthesize an amphiphilic triblock copolymer.
- The copolymer incorporated spiropyran (SP), hydroxyethyl methacrylate-glycine (HEMA-Gly), and N-isopropylacrylamide (NIPAAM) units.
- In vitro studies involved drug loading/release, cytotoxicity assays, cellular uptake imaging, ROS production analysis, and gene transfection efficiency tests.
Main Results:
- The nanocarrier demonstrated controlled doxorubicin (DOX) release under acidic conditions.
- Efficient cellular uptake and enhanced ROS production were observed in MDA-MB-231 TNBC cells.
- The system showed high gene transfection efficiency and selective Cu2+ ion sensing via fluorescence quenching.
Conclusions:
- The RAFT-synthesized triblock copolymer functions as a versatile theranostic platform for TNBC.
- The nanocarrier enables simultaneous drug release, gene transfection, ROS induction, and Cu2+-guided detection.
- This multifunctional platform shows promise for advanced TNBC diagnostics and combination therapy.
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