Tumor Microenvironment-Specific Chemical Internalization for Enhanced Gene Therapy of Metastatic Breast Cancer
作者机构：School of Pharmaceutical Sciences(Shenzhen)Sun Yat-sen UniversityShenzhen 518107China Paul C.Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Tianjin Key Laboratory of Biomedical MaterialsKey Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China
出 版 物：《Research》 (研究（英文）)
年 卷 期：2021年第2021卷第1期
页 面：689-703页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(81801843,81971737,31922042,and 81771966) the Guangdong Basic and Applied Basic Research Foundation(2020B1515020017) the Technology&Innovation Commission of Shenzhen Municipality(JCYJ20190807152601651) the Guangdong Special Support Program(2019TQ05Y224) the Fundamental Research Funds for the Central Universities(2020-RC320-002 and 2019PT320028).
摘 要：Benefiting from treating diseases at the genetic level,gene therapy has been considered a new revolution in the biomedical field.However,the extracellular and intracellular barriers during gene transport such as enzymatic degradation and endo-/lysosomal sequestration significantly compromise the therapeutic efficacy.Though photochemical internalization(PCI)has emerged as a promising approach for causing endo-/lysosomal leakage with translocation of the internalized molecules into the cytosol,its effect is still unsatisfactory due to the insufficient light penetration depth.Here,we develop tumor microenvironment-specific enhanced gene delivery by means of ROS generated from the in situ cascaded catalytic reactions in tumors involving GOx-mediated redox reaction and Mn2+-mediated Fenton-like reaction.The efficient enzymatic protection and successful endo-/lysosomal escape of cargo gene complexes have been demonstrated.Moreover,anti-Twist siRNA-loaded G@MMSNs-P exhibit tumor-specific biodegradation,excellent T1-weighted MR imaging,and significant inhibitory effects against breast cancer growth and pulmonary metastasis.
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