title: Subcellular-Scale Drug Transport via Ultrasound-Degradable Mesoporous Nanosilicon to Bypass Cancer Drug Resistance.
abstract: Delivering and releasing anticancer agents directly to their subcellular targets of action in a controlled manner are almost the ultimate goal of pharmacology, but it is challenging. In recent decades, plenty of efforts have been made to send drugs to tumor tissue or even specifically to cancer cells; however, at the subcellular scale, cancer cells have multiple cunning ways to hinder drugs from reaching their final action targets. Here, we demonstrate a strategy to bypass the last defense of cancer drug resistance by contolling the drug transportation and release at subcellular scale. We developed a platform based on ultrasound-degradable mesoporous nanosilicon, which allows drug delivery towards, ultrasound controlled drug release into the cell nucleus. This strategy altered the drug distribution within cells and remarkably enhanced the drug accumulation ratio at the action target, i.e. nucleus. In vitro and in vivo studies proved that this strategy reduced the drug dosage by an order of magnitude, prolonged drug retention and amplified therapeutic efficacy in tumor-bearing mice. These results offer new insights into bypassing cancer drug resistance through transport and release drugs directly to their action targets in a controlled manner.
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kang
authors.affiliation: Nanjing National Laboratory of Microstructures, School of Electronic Science and Engineering, Nanjing University, Nanjing, 210093, China.|School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225002, China.
authors.forename: Ming-Bo
authors.initials: MB
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Ji-Wu
authors.initials: JW
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
authors.forename: Jing-Juan
authors.initials: JJ
authors.lastname: Xu
authors.affiliation: Nanjing National Laboratory of Microstructures, School of Electronic Science and Engineering, Nanjing University, Nanjing, 210093, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D016503:Drug Delivery Systems; D065546:Drug Liberation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013347:Subcellular Fractions; D014463:Ultrasonography
chemical_list: D012822:Silicon Dioxide
keywords: drug delivery; drug resistance; mesoporous nanosilicon; subcellular transport; ultrasound