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

作　　者：Lingyu Qiu Shan Lei Jing Zhang Ruhan Yan Wansi Chen Jing Lin Wei-Guo Zhu Peng Huang 

机构地区：[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

出　　处：《Chinese Chemical Letters》2023年第9期235-242,共8页中国化学快报（英文版）

基　　金：financially supported by National Key R&D Program of China(Nos.2020YFA0908800,2018YFA0704000);Basic Research Program of Shenzhen(Nos.JCYJ20200109105620482,JCYJ20180507182413022);Shenzhen Science and Technology Program(No.KQTD20190929172538530)。

摘　　要：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 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R318[医药卫生—生物医学工程]