Nanoengineered sonosensitive platelets for synergistically augmented sonodynamic tumor therapy by glutamine deprivation and cascading thrombosis  

作　　者：Liqiang Zhou Wei Feng Yuhang Mao Yu Chen Xuanjun Zhang 

机构地区：[1]MOE Frontiers Science Center for Precision Oncology,Faculty of Health Sciences,University of Macao,Macao,SAR,999078,China [2]Materdicine Lab,School of Life Sciences,Shanghai University,Shanghai,200444,China [3]School of Medical Technology,Xi’an Medical College,Xi’an,710021,Shanxi,China

出　　处：《Bioactive Materials》2023年第6期26-36,共11页生物活性材料（英文）

基　　金：supported by the Science and Technology Development Fund,Macao SAR(Grant No.0114/2019/A2,0085/2020/A2);the Research Grant of University of Macao(Grant No.MYRG2020-00130-FHS).

摘　　要：Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration depth,which,unfortunately,suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms,such as glutathione(GSH)neutralization response to reactive oxygen species(ROS),and glutamine addictive properties of tumors.In this work,we developed a biological sonosensitive platelet(PLT)pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT.The amino acid transporter SLC6A14 blockade agentα-methyl-DL-tryptophan(α-MT)-loaded and MnO_(2)-coated porphyrinic metal-organic framework(MOF)nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs.When the sonosensitive PLT pharmacytes reached tumor sites through their natural tendencies to TME,US stimulated the PLTs-loaded porphyrinic MOF to generate ROS,resulting in morphological changes of the PLTs and the release of nanoparticles.Subsequently,intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release ofα-MT,which enabled the synergistically amplified SDT by inducing amino acid starvation,inhibiting mTOR,and mediating ferroptosis.In addition,US stimulation achieved the targeted activation of PLTs at tumor vascular site,which evolved from circulating PLTs to dendritic PLTs,effectively blocking the blood supply of tumors through thrombus formation,and revealing the encouraging potential to facilitate tumor therapeutics.

关 键 词：Sonosensitive platelets Glutamine deprivation Sonodynamic tumor therapy Amino acid starvation Drug delivery 

分 类 号：R318[医药卫生—生物医学工程]