Nature-Inspired Smart DNA Nanodoctor for Activatable In Vivo Cancer Imaging and In Situ Drug Release Based on Recognition-Triggered Assembly of Split Aptamer.
DNA-based activatable theranostic nanoprobes are still unmet for in vivo applications. Here, by utilizing the "induced-fit effect", a smart split aptamer-based activatable theranostic probe (SATP) was first designed as "nanodoctor" for cancer-activated in vivo imaging and in situ drug release. The SATP assembled with quenched fluorescence and stable drug loading in its free state. Once binding to target proteins on cell surface, the SATP disassembled due to recognition-triggered reassembly of split aptamers with activated signals and freed drugs. As proof of concept, split Sgc8c against CEM cancer was used for theranostic studies. Benefiting from the design without blocking aptamer sequence, the SATP maintained an excellent recognition ability similar to intact Sgc8c. An "incubate-and-detect" assay showed that the SATP could significantly lower background and improve signal-to-background ratio (∼4.8 times of "always on" probes), thus affording high sensitivity for CEM cell analysis with 46 cells detected. Also, its high selectivity to target cells was demonstrated in analyzing mixed cell samples and serum samples. Then, using doxorubicin as a model, highly specific drug delivery and cell killing was realized with minimized toxicity to nontarget cells. Moreover, in vivo and ex vivo investigations also revealed that the SATP was specifically activated by CEM tumors inside mice. Especially, contrast-enhanced imaging was achieved in as short as 5 min, thus, laying a foundation for rapid diagnosis and timely therapy. As a biocompatible and target-activatable strategy, the SATP may be widely applied in cancer theranostics.
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Yanli
Y
Lei
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Jinlu
J
Tang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Hui
H
Shi
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Xiaosheng
X
Ye
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Xiaoxiao
X
He
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Fengzhou
F
Xu
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Lv'an
L
Yan
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Zhenzhen
Z
Qiao
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province , Changsha 410082, China.
Kemin
K
Wang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000032:analysis*; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D061848:Optical Imaging; D000068936:Theranostic Nanomedicine
D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D004317:Doxorubicin; D004247:DNA