Porous Fe/Cu Nanoreactor with Dual Insurance Design for Precision Chemotherapy and Chemodynamic Therapy
Xianyu Zhu1,2, Lingli Gao3, Yanbo Zheng3
1Precision and Intelligence Medical Imaging Lab, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Rd., Xicheng Dist., Beijing, 100050, China.
Abstract:
Poor prognosis and chemotherapy response stem from difficulties in precise targeting and the lack of effective synergistic treatments. Nanozymes show promising potential in tumor chemodynamic therapy (CDT) by catalyzing hydrogen peroxide (H₂O₂) decomposition and glutathione depletion in the tumor microenvironment (TME). However, integrating precise chemotherapy targeting with CDT remains challenging. In this study, a porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) is developed for co-loading with the humanized 3F8 anti-GD2 disialoganglioside antibody (3F8) and the novel pyridazinone-based chemotherapeutic agent (IMB), forming a nanoreactor (3F8@FeCuNPs@IMB) for targeted chemotherapy and CDT. The nanoreactor responds specifically to the acidic TME as a primary insurance, allowing for the controlled release of IMB at the tumor site. The targeting antibody 3F8 coating on the surface of the nanozyme carrier acts as a secondary insurance, minimizing chemotherapy drug leakage during the delivery process and ensuring precise targeting for effective chemotherapy. Furthermore, FeCuNPs act as peroxidase-like (POD) and glutathione oxidase-like (GSHOX) enzymes, catalyzing hydroxyl radical (•OH) generation and depleting excess GSH, enhancing CDT. The results in vitro and in vivo indicate that the dual insurance designed 3F8@FeCuNPs@IMB offers a promising prospect for a targeted, precise, and effective combination of chemotherapy and CDT against melanoma.
Insights
This study developed a dual-targeted nanoreactor for melanoma treatment. It combines chemotherapy and chemodynamic therapy (CDT) for enhanced tumor targeting and efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Targeted drug delivery and synergistic treatments are crucial for improving cancer therapy outcomes.
- Nanozymes offer potential for tumor chemodynamic therapy (CDT) by modulating the tumor microenvironment (TME).
- Integrating precise chemotherapy with CDT remains a significant challenge in cancer treatment.
Purpose of the Study:
- To develop a nanoreactor for targeted chemotherapy and CDT against melanoma.
- To create a system that utilizes dual targeting and responds to the acidic tumor microenvironment for controlled drug release.
- To enhance the efficacy of cancer treatment by combining the strengths of chemotherapy and nanozyme-based CDT.
Main Methods:
- A porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) was synthesized.
- The nanozyme carrier was co-loaded with a chemotherapeutic agent (IMB) and an anti-GD2 antibody (3F8).
- The resulting nanoreactor (3F8@FeCuNPs@IMB) was evaluated for its targeting, drug release, and therapeutic effects in vitro and in vivo.
Main Results:
- The nanoreactor demonstrated specific response to the acidic TME, enabling controlled release of the chemotherapeutic agent.
- The 3F8 antibody provided precise tumor targeting, minimizing off-target drug effects.
- FeCuNPs exhibited peroxidase-like and glutathione oxidase-like activity, enhancing CDT through hydroxyl radical generation and glutathione depletion.
- In vitro and in vivo studies confirmed the synergistic efficacy of the combined chemotherapy and CDT approach against melanoma.
Conclusions:
- The developed dual-insurance nanoreactor (3F8@FeCuNPs@IMB) effectively combines targeted chemotherapy and CDT.
- This approach offers a promising strategy for precise and effective treatment of melanoma.
- The study highlights the potential of nanozyme-based nanoreactors in advancing cancer therapy.
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