Dual-Locked DNAzyme Platform for In Vitro and In Vivo Discrimination of Cancer Cells.
Xing HuangYanfei ZhangJun ChenLang ZhangYuzhi XuWen YinYakun ShiSi-Yang LiuXiaoyong ZouZong DaiPublished in: Analytical chemistry (2022)
Imaging of tumor-associated microRNAs (miRNAs) can provide abundant information for cancer diagnosis, whereas the occurrence of trace amounts of miRNAs in normal cells inevitably causes an undesired false-positive signal in the discrimination of cancer cells during miRNA imaging. In this study, we propose a dual-locked (D-locked) platform consisting of the enzyme/miRNA-D-locked DNAzyme sensor and the honeycomb MnO 2 nanosponge (hMNS) nanocarrier for highly specific cancer cell imaging. For a proof-of-concept demonstration, apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 were chosen as key models. The hMNS nanocarrier can efficiently release the D-locked DNAzyme sensor in living cells due to the decomposition of hMNS by glutathione, which can also supply Mn 2+ for DNAzyme cleavage. Ascribing to the smart design of the D-locked DNAzyme sensor, the fluorescence signal can only be generated by the synergistic response of APE1 and miR-21 that are overexpressed in cancer cells. Compared with the miRNA single-locked DNAzyme sensor and the small-molecule (ATP)/miRNA D-locked DNAzyme sensor, the proposed enzyme (APE1)/miRNA D-locked DNAzyme sensor exhibited 2.6-fold and 2.4-fold higher discrimination ratio ( F cancer / F normal ) for cancer cell discrimination, respectively. Owing to the superior performance, the D-locked strategy can selectively generate a fluorescence signal in cancer cells, facilitating accurate discrimination of cancer both in vitro and in vivo . Furthermore, this D-locked platform is easily adaptable toward other target molecules by redesigning the DNA sequences. The outstanding performance and expansibility of this D-locked platform holds promising prospects for cancer diagnosis and related biomedical applications.
Keyphrases
- living cells
- single molecule
- fluorescent probe
- papillary thyroid
- high resolution
- small molecule
- label free
- squamous cell
- high throughput
- cell proliferation
- squamous cell carcinoma
- drug delivery
- induced apoptosis
- healthcare
- long noncoding rna
- cell free
- young adults
- oxidative stress
- cancer therapy
- endoplasmic reticulum stress
- risk assessment
- childhood cancer
- room temperature
- single cell
- nucleic acid