title: Near Infrared-Guided Smart Nanocarriers for MicroRNA-Controlled Release of Doxorubicin/siRNA with Intracellular ATP as Fuel.
abstract: In chemotherapy, it is a great challenge to recruit endogenous stimuli instead of external intervention for targeted delivery and controlled release; microRNAs are the most promising candidates due to their vital role during tumorigenesis and significant expression difference. Herein, to amplify the low abundant microRNAs in live cells, we designed a stimuli-responsive DNA Y-motif for codelivery of siRNA and Dox, in which the cargo release was achieved via enzyme-free cascade amplification with endogenous microRNA as trigger and ATP (or H(+)) as fuel through toehold-mediated strand displacement. Furthermore, to realize controlled release in tumor cells, smart nanocarriers were constructed with stimuli-responsive Y-motifs, gold nanorods, and temperature-sensitive polymers, whose surfaces could be reversibly switched between PEG and RGD states via photothermal conversion. The PEG corona kept the nanocarriers stealth during blood circulation to protect the Y-motifs against nuclease digestion and enhance passive accumulation, whereas the exposed RGD shell under near-infrared (NIR) irradiation at tumor sites facilitated the specific receptor-mediated endocytosis by tumor cells. Through modulating NIR laser, microRNA, or ATP expressions, the therapy efficacies to five different cell lines were finely controlled, presenting NIR-guided accumulation, massive release, efficient gene silence, and severe apoptosis in HeLa cells; in vivo study showed that a low dosage of nanocarriers synergistically inhibited the tumor growth by silencing gene expression and inducing cell apoptosis under mild NIR irradiation, though they only brought minimum damage to normal organs. The combination of nanomaterials, polymers, and DNA nanomachines provided a promising tool for designing smart nanodevices for disease therapy.
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Anqi
authors.initials: A
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Linting
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Qianhao
authors.initials: Q
authors.lastname: Min
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Zhu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D061848:Optical Imaging; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D035683:MicroRNAs; D034741:RNA, Small Interfering; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D004247:DNA
keywords: DNA nanomachine; aptamer; drug delivery; microRNA; smart nanocarriers