2D antimonene-integrated composite nanomedicine for augmented low-temperature photonic tumor hyperthermia by reversing cell thermoresistance  

作　　者：Jianrong Wu Xiaojun Cai Gareth R.Williams Zheying Meng Weijuan Zou Li Yao Bing Hu Yu Chen Yuanyi Zheng 

机构地区：[1]Department of Ultrasound in Medicine,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai,200233,PR China [2]UCL School of Pharmacy,University College London,London,WC1N 1AX,UK [3]Materdicine Lab,School of Life Sciences,Shanghai University,Shanghai,200050,PR China [4]State Key Laboratory of Oncogenes and Related Genes,School of Medicine,Shanghai Jiao Tong University,Shanghai,200233,PR China

出　　处：《Bioactive Materials》2022年第4期295-305,共11页生物活性材料（英文）

基　　金：the financial support from the NSFC Key Projects of International Cooperation and Exchanges(Grant No.81720108023);National Key R&D Program of China(Grant No.2018YFC0115200);National Natural Science Foundation of China(Grant No.82001943);Translational medicine national science and technology infrastructure(Shanghai)open project fund(TMSK-2020-004);China Postdoctoral Science Foundation(2020M681331,2021T140458).

摘　　要：The overexpression of heat shock proteins(HSPs)in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments,inducing thermoresistance and thus diminishing the treatment efficacy.Here,we report a distinct“non-inhibitor involvement”strategy to address this issue through engineering a calcium-based nanocatalyst(G/A@CaCO_(3)-PEG).The constructed nanocatalyst consists of calcium carbonate(CaCO_(3))-supported glucose oxidase(GOD)and 2D antimonene quantum dots(AQDs),with further surface modification by lipid bilayers and polyethylene glycol(PEG).The engineered G/A@CaCO_(3)-PEG nanocatalyst features prolonged blood circulation,which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment,resulting in rapid release of drug cargo in the tumor microenvironment.The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate(ATP)and subsequent down-regulation of HSP expression.This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells’thermoresistance.Consequently,synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy.Systematic in vitro and in vivo evaluations have demonstrated that G/A@CaCO_(3)-PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate(83.92%).This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply.

关 键 词：Antimonene Heat shock proteins Photothermal therapy Glucose oxidase Calcium carbonate 

分 类 号：R730.5[医药卫生—肿瘤] R318[医药卫生—临床医学]