HDAC6 inhibitor loaded bimetallene nanosheets with antagonizing thermoresistance for augmented mild photothermal therapy |
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| Institution: | 1. Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen 518055, China;2. Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, International Cancer Center, Shenzhen University Medical School, Shenzhen 518055, China;3. Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China;1. CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institutes, Chinese Academy of Sciences, Xiamen 361021, China;4. State Key Laboratory of Structure Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China;5. Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China, Fuzhou 350108, China;1. Laboratory of Environmental Sciences and Technology, Xinjiang Technical Institute of Physics & Chemistry, and Key Laboratory of Functional Materials and Devices for Special Environments, Chinese Academy of Sciences, Urumqi 830000, China;2. Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China;3. Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, China;1. College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China;2. CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China;1. Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523058, China;2. Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523058, China;3. Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China;4. Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan 528000, China;1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;2. Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China;1. School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China;2. Department of Chemistry, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland;3. State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China |
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| Abstract: | Photothermal therapy (PTT) induces thermoresistance through cellular heat shock response, which impairs the therapeutic efficacy of the PTT. To resolve this problem, we developed a photothermal theranostics (denoted as PMH), which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6 (HDAC6) selected inhibitor (ACY-1215), showing the synergistic antitumor effect both in vitro and in vivo. Mechanistically, under the photoacoustic imaging (PA) navigation, the released ACY-1215 triggered by NIR laser irradiation decrease the heat shock proteins (HSPs) expression and weaken the HDAC6-regulated HSP90 deacetylation, thus hindering the degradation of PTT-induced misfolded or unfold proteins through proteasome dependent pathway. Moreover, mild photothermal therapy (mPTT) treatment compromised the autophagy, which induced by HDAC6 inhibition, leading to mPTT-induced misfolded or unfold proteins further accumulation. Given that inhibition of HDAC6 plus mPTT contribute to tumor eradication. This study develops a promising combination strategy based on mPTT for future cancer treatment. |
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