DNA Polymerase-Directed Hairpin Assembly for Targeted Drug Delivery and Amplified Biosensing.
Due to the predictable conformation and programmable Watson-Crick base-pairing interactions, DNA has proven to be an attractive material to construct various nanostructures. Herein, we demonstrate a simple model of DNA polymerase-directed hairpin assembly (PDHA) to construct DNA nanoassemblies for versatile applications in biomedicine and biosensing. The system consists of only two hairpins, an initiator and a DNA polymerase. Upon addition of aptamer-linked initiator, the inert stems of the two hairpins are activated alternately under the direction of DNA polymerase, which thus grows into aptamer-tethered DNA nanoassemblies (AptNAs). Moreover, through incorporating fluorophores and drug-loading sites into the AptNAs, we have constructed multifunctional DNA nanoassemblies for targeted cancer therapy with high drug payloads and good biocompatibility. Interestingly, using the as-prepared AptNAs as building blocks, DNA nanohydrogels are self-assembled after centrifugation driven by liquid crystallization and dense packaging of DNA duplexes. Taking advantage of easy preparation and high loading capacity, the PDHAs are readily extended to the fabrication of a label-free biosensing platform, achieving amplified electrochemical detection of microRNA-21 (miR-21) with a detection limit as low as 0.75 fM and a dynamic range of 8 orders of magnitude. This biosensor also demonstrates excellent specificity to discriminate the target miR-21 from the control microRNAs and even the one-base mismatched one and further performs well in analyzing miR-21 in MCF-7 tumor cells.
State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, China.
Yingying
Y
Wang
State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, China.
Li-Ping
LP
Jiang
State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, China.
Shiwei
S
Zhou
State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, China.|Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, College of Chemistry and Chemical Engineering, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Laboratory of Fiber Materials and Modern Textiles, the Growing Base for State Key Laboratory, Qingdao University , Qingdao 266071, China.
Sai
S
Bi
State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, China.
Jun-Jie
JJ
Zhu
D015374:Biosensing Techniques; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D016503:Drug Delivery Systems; D057230:Limit of Detection; D049329:Nanostructures
D004247:DNA; D004259:DNA-Directed DNA Polymerase
DNA nanoassembly; cancer cell; drug delivery; microRNA; signal amplification