Human HSP70 Promoter‐Based Prussian Blue Nanotheranostics for Thermo‐Controlled Gene Therapy and Synergistic Photothermal Ablation |
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Authors: | Yajuan Liu Guiming Shu Xue Li Hongbin Chen Bo Zhang Huizhuo Pan Tao Li Xiaoqun Gong Hanjie Wang Xiaoli Wu Yan Dou Jin Chang |
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Affiliation: | 1. School of Life Sciences, Health Science Platform, Tianjin University, Tianjin Engineering Research Center for Micro‐Nano Biomaterials and Detection‐Treatment Technology, Tianjin, P. R. China;2. Tianjin Enterprises Key Laboratory of Blood Perfusion Technology, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin Third Central Hospital, Tianjin, P. R. China;3. Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, P. R. China;4. Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, P. R. China |
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Abstract: | Realizing precise control of the therapeutic process is crucial for maximizing efficacy and minimizing side effects, especially for strategies involving gene therapy (GT). Herein, a multifunctional Prussian blue (PB) nanotheranostic platform is first designed and then loaded with therapeutic plasmid DNA (HSP70‐p53‐GFP) for near‐infrared (NIR) light‐triggered thermo‐controlled synergistic GT/photothermal therapy (PTT). Due to the unique structure of the PB nanocubes, the resulting PB@PEI/HSP70‐p53‐GFP nanoparticles (NPs) exhibit excellent photothermal properties and pronounced tumor‐contrast performance in T1/T2‐weighted magnetic resonance imaging. Both in vitro and in vivo studies demonstrate that mild NIR‐laser irradiation (≈41 °C) activates the HSP70 promoter for tumor suppressor p53‐dependent apoptosis, while strong NIR‐laser irradiation (≈50 °C) induces photothermal ablation for cellular dysregulation and necrosis. Significant synergistic efficacy can be achieved by adjusting the NIR‐laser irradiation (from ≈41 to ≈50 °C), compared to using GT or PTT alone. In addition, in vitro and in vivo toxicity studies demonstrate that PB@PEI/HSP70‐p53‐GFP NPs have good biocompatibility. Therefore, this work provides a promising theranostic approach for controlling combined GT and PTT via the heat‐shock response. |
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Keywords: | gene therapy human HSP70 promoter nanotheranostics photothermal effect Prussian blue nanocubes |
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