Poly(2-(diethylamino)ethyl methacrylate)-Functionalized Carbon Nanodots as Theranostic Platforms for siRNA Delivery and Survivin Silencing in Triple-Negative Breast Cancer.

Abstract

This study describes the development of carbon nanodot (CDs)-based theranostic nanocarriers that integrate gene silencing with fluorescence imaging. Nitrogen- and sulfur-doped CDs were functionalized through controlled radical surface polymerization of 2-(diethylamino)ethyl methacrylate (DEAEMA), yielding self-tracking, cationic siRNA carriers CDs-pDEAEMA. The functionalization of CDs enhanced their fluorescence, broadening the emission spectrum toward the biologically transparent window. Fluorescent CDs-pDEAEMA effectively bound siRNA, remaining stable under physiological conditions, while in vitro studies proved their hemocompatibility and cytocompatibility on human dermal fibroblasts. Moreover, the ability to deliver BIRC5 siRNA was demonstrated in MDA-MB-231, successfully transfecting triple-negative breast cancer cells and resulting in an 80% reduction in the anti-apoptotic protein survivin. Furthermore, uptake studies demonstrated that the theranostic CDs are efficiently internalized in tumor cells and are clearly detectable by fluorescence imaging in the red region. These findings highlight the potential of CDs-pDEAEMA as an advanced theranostic tool for real-time tracking of siRNA therapy of breast cancer.