Near Infrared-Guided Smart Nanocarriers for MicroRNA-Controlled Release of Doxorubicin/siRNA with Intracellular ATP as Fuel.
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.
['Zhang|Penghui|P|', 'Wang|Chen|C|', 'Zhao|Jingjing|J|', 'Xiao|Anqi|A|', 'Shen|Qi|Q|', 'Li|Linting|L|', 'Li|Jianxin|J|', 'Zhang|Junfeng|J|', 'Min|Qianhao|Q|', 'Chen|Jiangning|J|', 'Chen|Hong-Yuan|HY|', 'Zhu|Jun-Jie|JJ|']
D000255:Adenosine Triphosphate D000818:Animals D000903:Antibiotics, Antineoplastic D045744:Cell Line, Tumor D004247:DNA D003692:Delayed-Action Preparations D004317:Doxorubicin D016503:Drug Delivery Systems D005260:Female D006801:Humans D051379:Mice D008819:Mice, Nude D035683:MicroRNAs D041681:NIH 3T3 Cells D009369:Neoplasms D061848:Optical Imaging D034741:RNA, Small Interfering
smart nanocarriers microRNA DNA nanomachine aptamer drug delivery