Three-in-one DNA nanowheels for simultaneous tumor regression and drug resistance prevention in breast cancer model  

作　　者：Ping Li Chun-Feng Feng Peng-Fei Lyu Fei Liu Hui-Sheng Li Li-Qun Zhang 

机构地区：[1]Department of Maxillofacial and Ear,Nose and Throat Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Basic and Translational Medicine on Head&Neck Cancer,Tianjin,China [2]Department of Clinical Laboratory,The Second Affiliated Hospital,Army Medical University,Chongqing,China [3]Department of Breast Oncology Department,Tianjin Medical University Cancer Institute and Hospital,Tianjin,China

出　　处：《Advanced Sensor and Energy Materials》2024年第3期2-10,共9页先进传感器与能源材料（英文）

基　　金：financially supported by National Natural Science Foundation of China(Grant No.81873981 and 81772284);the Excellent Young Talents Fund Program of TJMUCH(Grant No.2019-1-11);Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).

摘　　要：Herein,we proposed novel three-in-one DNA nanowheels with simultaneous chemo and gene therapy to treat tumor,especially to prevent simultaneous drug resistance,which could be disassembled via a cascaded hybridization reactions triggered by the highly expressed microRNA in cancer cells for smart and efficient cancer therapy.Typically,with breast cancer as a model,microRNA 21 could trigger the self-disassembly of DNA nanowheel 1 via hybridization with a specially designed oligonucleotide(anti-microRNA 21)in DNA nanowheel 1,releasing another special oligonucleotide(Contact sequence)to trigger the self-disassembly of DNA nanowheel 2 with releasing of a special oligonucleotide(anti-Contact sequence)to trigger the self-disassembly of DNA nanowheel 1 cyclically,and thus the cascaded hybridization reactions with three-in-one anti-cancer functions could be generated based on three main therapeutic effects via releasing doxorubicin to inhibit macromolecular biosynthesis,antisense oligonucleotide of microRNA 21 to activate the apoptotic cell pathway and antisense oligonucleotide of MDR1 to prevent the drug resistance respectively.As expected,the proposed method showed improved therapeutic efficacy on the cancer cells with about 80%apoptosis ratio,especially on the drug resistant cancer cells with about 75%apoptosis ratio,compared with that in the conventional anti-cancer systems of about 70%on cancer cells and below 40%on drug resistant cancer cells,respectively.Most importantly,this strategy opened the door for generation of complex functional DNA-based structures for target triggering drugs releasing system combining with chemo-and genetherapy to generate tumor regression and prevent drug resistance with an optimized therapeutic efficacy,providing a new avenue for efficient cancer treatment,especially drug resistant cancers.

关 键 词：DNA machine Drug resistance Multi-combination strategy Self-disassembly 

分 类 号：R73[医药卫生—肿瘤]