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Dual-Responsive Triple-Synergistic Fe-MOF for Tumor Theranostics
Summary:
The authors from Xiamen University, Harvard University, and Massachusetts Institute of Technology developed a near-infrared and pH dual-responsive Fe-MOF material (PCN-DOX@PDA) with excellent biocompatibility and antitumor ability, achieving good results in the application of tumor theranostics.
Background:
1. To address the problem of poor antitumor efficiency in most antitumor methods based on drug delivery systems, previous researchers developed various intelligent responsive drug delivery systems and combined therapeutic methods, but single-response systems have insufficient drug release, and single chemotherapy has issues like adverse systemic toxicity.
2. The authors in this study proposed constructing a near-infrared and pH dual-response multimodal collaborative platform (PCN-DOX@PDA) for tumor diagnosis and treatment, realizing MRI-mediated chemotherapy, photothermal, and photodynamic synergistic therapy with excellent performance.
Research Content:
1. Synthesis:
The authors synthesized PCN-600 first, modified it with DMSA, then coated it with PDA through dopamine self-polymerization to get PCN@PDA, and further loaded DOX to obtain PCN-DOX@PDA using methods involving hydrothermal reaction, amidation reaction, and self-assembly.
2. Characterizations:
1) TG analysis showed the PDA shell accounts for 18.5 wt %.
2) SEM/TEM tests show the particle size of PCN-600 is about 150 nm, and PCN@PDA is around 180 nm with a core/shell structure; hydrodynamic particle size of PCN@PDA is about 260 nm.
3) XRD confirmed the crystal structure of PCN-600 and PCN@PDA; zeta potential tests showed changes after modifications; Vis-NIR absorption spectra indicated PCN@PDA has higher absorption in 550-900 nm; MRI tests showed PCN-DOX@PDA has an r₂ value of 32.84 mM⁻¹s⁻¹.
3. Application:
The material was tested in in vitro and in vivo antitumor applications. In vitro, it showed high drug-loading efficiency (up to 78%), pH and NIR-responsive drug release, good photothermal and photodynamic effects, and significant cytotoxicity to 4T1 cells under dual light irradiation. In vivo, on 4T1 tumor-bearing mice, it achieved almost complete tumor ablation with good biocompatibility.
4. Mechanism:
Under 633 nm laser, TCPP in PCN-600 generates singlet oxygen (¹O₂) for photodynamic therapy (PDT); PDA acts as a photothermal agent for photothermal therapy (PTT). The weak acidity of the tumor microenvironment and NIR-induced heat promote DOX release for chemotherapy. Fe³⁺ in PCN enables MRI. The triple synergism enhances antitumor effect by combining these mechanisms.
Outlook:
This research successfully developed a dual-responsive triple-synergistic Fe-MOF platform, which has great significance for precision cancer therapy and diversified biomedical applications, providing an efficient and safe multimodal tumor therapy strategy.
Dual-Responsive Triple-Synergistic Fe-MOF for Tumor Theranostics
Authors: Zhiwei Chen, Yaoji Sun, Jiawei Wang, Xi Zhou, Xiangjian Kong, Jiashen Meng, Xingcai Zhang
DOI：10.1021/acsnano.2c10310
Link：https://pubs.acs.org/doi/10.1021/acsnano.2c10310
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