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HDAC6 inhibitor loaded bimetallene nanosheets with antagonizing thermoresistance for augmented Mild photothermal therapy

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中国化学快报:英文版 2023年第9期34卷 235-242页

作者： Lingyu Qiu Shan Lei Jing Zhang Ruhan Yan Wansi Chen Jing Lin Wei-Guo Zhu Peng Huang Guangdong Key Laboratory of Genome Instability and Human Disease Prevention Department of Biochemistry and Molecular BiologyShenzhen University Medical SchoolShenzhen 518055China Base for International Science and Technology Cooperation:Carson Cancer Stem Cell Vaccines R&D Center International Cancer CenterShenzhen University Medical SchoolShenzhen 518055China Marshall Laboratory of Biomedical Engineering International Cancer CenterLaboratory of Evolutionary Theranostics(LET)School of Biomedical EngineeringShenzhen University Medical SchoolShenzhen 518060China

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 mPTTinduced misfolded or unfold proteins further accumulation.Given that inhibition of HDAC6 plus m PTT contribute to tumor eradication.This study develops a promising combination strategy based on m PTT for future cancer treatment.

关键词： Mild photothermal therapy Thermoresistance Histone deacetylase 6 Heat shock proteins Autophagy

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Robust boron nanoplatform provokes potent tumoricidal activities via inhibiting heat shock protein

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Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 728-740页

作者： Yuying Zhao Ning Liu Piaoxue Liu Taojian Fan Rui Ma Huijie Hong Xiaojia Chen Zhongjian Xie Han Zhang Qi Wang Tongkai Chen Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou 510405China Institute of Microscale Optoelectronics Collaborative Innovation Centre for Optoelectronic Science&TechnologyKey Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong ProvinceCollege of Physics and Optoelectronic EngineeringShenzhen Key Laboratory of Micro-Nano Photonic Information TechnologyGuangdong Laboratory of Artificial Intelligence and Digital Economy(SZ)Shenzhen UniversityShenzhen 518060China College of Health Science and Environmental Engineering School of Shenzhen Technology UniversityShenzhen 518118China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Institute of Pediatrics Shenzhen Children’s HospitalShenzhen 518038China Shenzhen International Institute for Biomedical Research Shenzhen 518116China

Near-infrared(NIR)-light-triggered photothermal therapy(PTT)is a promising treatment for breast cancer.However,its therapeutic efficiency is often compromised due to the heatinduced up-regulation of heat shock proteins,which confer photothermal resistance.To solve this urgent problem,PEGylated two-dimensional boron nanosheets(B-PEG)-which allow both multimodal imaging and photothermal conversion-were loaded with gambogic acid(GA),which can inhibit heat shock protein 90(Hsp90).Experimental findings indicated that this combination of B-PEG and GA could serve as an integrated drug delivery system for cancer diagnosis and treatment.It could be used to administer mild PTT as well as chemotherapy for breast cancer,provide improved anti-tumor effects,and reduce the toxicity of PTT,all while inhibiting breast cancer growth.This drug delivery system could offer a novel tool for administering chemotherapy combined with PTT while avoiding the adverse effects of traditional PTT.

关键词： Mild photothermal therapy Chemotherapy Boron nanosheets Heat shock proteins Breast cancer

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