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

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.

Nanoplatform-based cellular reactive oxygen species regulation for enhanced oncotherapy and tumor resistance alleviation

The cancer cells realize their proliferation and metastasis activities based on the special redox adaptation to increased reactive oxygen species(ROS)level,which inversely makes them sensitive to external interference with their redox state.In view of this,in recent decades,researchers have made great efforts to construct a series of novel nanoplatform-based ROS-mediated cancer therapies through increasing ROS generation and inhibiting the ROS elimination.Besides,the multidrug resistance and thermoresistance of tumor are closely related to tumor redox state.Recently,numerous works have shown that ROS regulation in cancer cells can intervene in the expression,function and stability of related proteins to achieve reversal of tumor resistance.In this review,the recent researches about ROS-regulating nanoagents on cancer therapy and tumor resistance alleviation have been well summarized.Finally,the challenges and research directions of ROS-regulating nanoagents for future clinical translation are also discussed.