Circular RNA Targeted Theranostic Nanoplatform for Liver Cancer-Related Gene Detection and Metastasis Regulation in Zebrafish Using Optical Sensing and Imaging

Liver cancer (LC) is the third leading cause of cancer deaths worldwide, with the unsatisfactory clinical outcome due to high heterogeneity and metastasis. Unfortunately, it is still great challenging to achieve both effective screening and precise treatment of LC. Herein, a nanocomposite integrating dual-optical probes and gene regulation sequence was designed and prepared to simultaneously detect the novel gene biomarker and inhibit the metastasis-related gene function, achieving dual diagnostic and treatment functions for LC. Using the biosensing model based on surface-enhanced Raman spectroscopy (SERS) and fluorescence imaging, different expression of target circular RNA (cSMARCA5) in normal and LC cells can be characterized and quantified with an ultra-low limit of detection of 4.50 fM. Meanwhile, the specially-designed sequence loaded in the nanocomposite is capable of inhibiting the migration and invasion of LC cells in an in vitro model. Moreover, its ability of metastasis regulation for potential gene therapy can be further confirmed using optical imaging method via in vivo zebrafish transplantation tumor model. This work presents a dual-function nano-platform for simultaneous optical screening and gene treatment of LC, providing a unique strategy for precise medicine.