AuNPs/DNAzyme/siRNA three-dimensional nanomotor for CEACAM6 RNA detection in cerebrospinal fluid and gene therapy of NSCLC

Abstract

Non-small-cell lung cancer (NSCLC), with the most challenging problem of leptomeningeal metastasis (LM), is the most prevalent malignancy worldwide. Our previous research found that carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) serve as a potential biomarker in NSCLC-LM. Which is also a therapeutic target for NSCLC and related to cell migration, invasion, and metastasis. Herein, we first constructed a diagnostic and treatment-integrated Au NPs/DNAzyme/siRNA nanoplatform to detect the CEACAM6 RNA in cerebrospinal fluid and living cells, and inhibit tumor growth by gene therapy. The nanoprobe would be triggered by CEACAM6 RNA and the fluorescence signal would be amplified by DNAzyme cyclic reaction for in-situ imaging. The sensitivity and specificity of Au nanoprobe for the detection of CSF samples were 83.33% and 91.67%, respectively. The delivery of siRNA by Au NPs can enhance its uptake and accumulation by tumor cells, leading to a down-regulation of the CEACAM6 protein and ultimately inhibiting the invasion and migration of tumor cells. Furthermore, this nanoprobe have been effectively implemented for in-situ fluorescence imaging and tumor growth inhibition in mice models. It is undoubted that such a combination nanoplatform would be a promising diagnosis and treatment-integrated strategy for potential biomarker detection and cancer therapy.