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Theranostic nanosystem with supramolecular self-assembly for enhanced reactive oxygen species-mediated apoptosis
Dan Yan1, Haili Zhang1, Xiao Xu1
1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Abstract:
With the development of precision medicine, visual and traceable treatments are highly desirable for cancer therapy. However, researchers and clinicians remain confused regarding where the drug distributes and location of the tumor, when the drug is released and when to irradiate the tumor, and how the drug presents antitumor activity, all of which hinders assessment of the cancer patient's condition and formulation of a follow-up treatment scheme for clinicians. Here, a supramolecular self-assembly theranostic nanosystem (MWNs) was designed for enhanced reactive oxygen species (ROS)-mediated cell apoptosis guided by dual-modality tumor imaging. Specifically, merocyanine was introduced in cyanine dye to extend its conjugated π-scaffolds, which could preferentially self-assemble into nanovesicles owing to its amphipathy. Furthermore, withaferin A (WA), used as a chemotherapeutic drug, was loaded to construct MWNs. The assembled or disassembled MWNs behaved differently in photoacoustic (PA) intensity and fluorescence signal intensity. The MWNs exhibited stronger PA signals and quenched fluorescence, which monitors their distribution and images the tumor location in vivo, while the disassembled MWNs showed weak PA signals and recovered fluorescence, indicating the release of drug and instructing the appropriate time to irradiate for photodynamic therapy (PDT). Thus, ROS generation introduced by PDT and released WA led to cell apoptosis. This intelligent nanosystem for precise cancer therapy that reveals where the tumor is, when to irradiate the tumor, and how the tumor is cured might establish the basis for biomedical applications of finely controlled platform.
Insights
A new theranostic nanosystem (MWNs) enables dual-modality tumor imaging for precise cancer therapy. This system visualizes tumor location and drug release, guiding photodynamic therapy (PDT) and chemotherapy for enhanced apoptosis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Precision medicine demands visual and traceable cancer therapies.
- Current limitations in tracking drug distribution, tumor location, drug release, and treatment timing hinder effective cancer patient management.
- There is a need for integrated systems that provide real-time monitoring and guidance for cancer treatment.
Purpose of the Study:
- To design a supramolecular self-assembly theranostic nanosystem (MWNs) for dual-modality tumor imaging.
- To enable enhanced reactive oxygen species (ROS)-mediated cancer cell apoptosis.
- To provide visual cues for drug release and optimal timing for photodynamic therapy (PDT).
Main Methods:
- Fabrication of MWNs using merocyanine-based amphipathic molecules and loading with withaferin A (WA).
- Utilizing changes in photoacoustic (PA) and fluorescence signals to monitor MWN assembly/disassembly, drug release, and tumor location.
- Investigating ROS generation via PDT and chemotherapy-induced cell apoptosis.
Main Results:
- MWNs demonstrated strong PA signals and quenched fluorescence for in vivo tumor imaging and distribution tracking.
- Disassembly of MWNs correlated with drug release, indicated by weak PA signals and recovered fluorescence, signaling optimal PDT timing.
- The combined effect of PDT-induced ROS and released WA promoted cancer cell apoptosis.
Conclusions:
- The developed MWNs function as an intelligent nanosystem for precise cancer therapy.
- This theranostic platform offers visual guidance for tumor location, treatment timing, and therapeutic efficacy assessment.
- The study lays the groundwork for advanced biomedical applications utilizing finely controlled theranostic platforms.
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