Activable Photodynamic DNA Probe with an“AND”Logic Gate for Precision Skin Cancer Therapy  

作　　者：Jiaojiao Zhu Lanyuan Peng Shah Jehan Haiyang Wang Xiang Chen Shuang Zhao Wenhu Zhou 

机构地区：[1]Xiangya School of Pharmaceutical Sciences,Central South University,Changsha,Hunan 410013,China [2]Department of Dermatology,Hunan Engineering Research Center of Skin Health and Disease,Hunan Key Laboratory of Skin Cancer and Psoriasis,Xiangya Hospital,Central South University,Changsha,Hunan 410008,China [3]Key Laboratory of Biological Nanotechnology of National Health Commission,Changsha,Hunan 410008,China. [4]Furong Laboratory,Changsha,Hunan,China [5]Department of Vascular Surgery,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510120,China.

出　　处：《Research》2024年第3期735-750,共16页研究（英文）

基　　金：the Natural Science Foundation of Hunan Province in China(2021JJ20084)and the Science and Technology Innovation Program of Hunan Province(2021RC3020).

摘　　要：Photodynamic therapy(PDT)has emerged as a promising approach for squamous cell carcinoma treatment but hindered by tumor hypoxia,acquired resistance,phototoxicity,and so on.To address these issues,we developed a smart strategy utilizing activable photosensitizers delivered by an aptamer-functionalized DNA probe(ADP).The ADP incorporated an AS1411 aptamer for tumor targeting and a linear antisense oligonucleotide(ASO)for recognition of Survivin mRNA.In the absence of the target,PDT remained quenched,thereby avoiding phototoxicity during circulation and nonselective distribution.With the aid of the aptamer,ADP achieved selective targeting of tumors.Upon internalization,ADP targeted recognized Survivin mRNA,triggering PDT activation,and releasing ASO to down-regulate Survivin expression and reverse tumor resistance.Consequently,the activable photosensitizers exhibited an“AND”logic gate,combining tumor-targeting delivery and tumor-related gene activation,thus enhancing its specificity.Additionally,the incorporation of hemin into the ADP provided catalase activity,converting tumor-abundant H_(2)O_(2) into O_(2),thereby ameliorating tumor hypoxia.The resulting functionalized G-quadruplex/hemin–DNA probe complex demonstrated targeted delivery and activation,minimized side effects,and enhanced PDT efficacy in both xenograft tumor-bearing mice and patient-derived xenograft models.This study offers a unique and promising platform for efficient and safe PDT,thus holding great potential for future clinical translation and improved cancer therapy.

关 键 词：SPECIFICITY thereby SKIN 

分 类 号：R739.5[医药卫生—肿瘤]