STAT3-specific nanocarrier for shRNA/drug dual delivery and tumor synergistic therapy  

作　　者：Le Sun Jishang Sun Cuiyao Li Keying Wu Zhiyang Gu Lan Guo Yi Zhou Baoqin Han Jing Chang 

机构地区：[1]College of Marine Life Science,Ocean University of China,Qingdao,266003,PR China [2]Laboratory for Marine Drugs and Bioproducts,Qingdao Marine Science and Technology Center,Qingdao,266237,PR China

出　　处：《Bioactive Materials》2024年第11期137-157,共21页生物活性材料（英文）

基　　金：Shandong Provincial Key Research and Development Program(Major Scientific and Technological Innovation Project,No.2022CXGC010505);National Natural Science Foundation of China(No.51773188);National Key Research and Development Program of China(No.2023YFC2812004);Key Project of Natural Science Foundation of Shandong Province(No.ZR2020KE016).

摘　　要：Non-small cell lung cancer(NSCLC)is a major disease with high incidence,low survival rate and prone to develop drug resistance to chemotherapy.The mechanism of secondary drug resistance in NSCLC chemotherapy is very complex,and studies have shown that the abnormal activation of STAT3(Signal Transducer and Activator of Transcription 3)plays an important role in it.In this study,the pGPU6/GFP/Neo STAT3-shRNA recombinant plasmid was constructed with STAT3 as the precise target.By modifying hydrophilic and hydrophobic blocks onto chitosan,a multifunctional vitamin E succinate-chitosan-polyethylene glycol monomethyl ether histidine(VES-CTS-mPEG-His)micelles were synthesized.The micelles could encapsulate hydrophobic drug doxorubicin through self-assembly,and load the recombinant pGPU6/GFP/Neo STAT3-shRNA(pDNA)through positive and negative charges to form dual-loaded nanoparticles DOX/VCPH/pDNA.The co-delivery and synergistic effect of DOX and pDNA could up-regulate the expression of PTEN(Phosphatase and Tensin Homolog),down-regulate the expression of CD31,and induce apoptosis of tumor cells.The results of precision targeted therapy showed that DOX/VCPH/pDNA could significantly down-regulate the expression level of STAT3 protein,further enhancing the efficacy of chemotherapy.Through this study,precision personalized treatment of NSCLC could be effectively achieved,reversing its resistance to chemotherapy drugs,and providing new strategies for the treatment of drug-resistant NSCLC.

关 键 词：Synergistic therapy Short hairpin RNA STAT3 signaling pathway Drug delivery Tumor treatment 

分 类 号：R730.5[医药卫生—肿瘤]