Stimuli responsive nanogels with intrinsic fluorescence: Promising nanovehicles for controlled drug delivery and cell internalization detection in diverse cancer cell lines

Abstract Nanogels are an important class of nanomaterials with a wide field of potential applications in nanomedicine. Fluorescent nanogels have the great advantage of the application in theranostics. In this study, intrinsic fluorescent nanogels, crosslinked with fluorescein O,O′-diacrylate (FDA), were synthetized and studied for first time, via a robust methodology of one–pot, resulting in yields in scale of grams. This new type of nanovehicles avoid the susceptibility to leaching, inhomogeneity, or degradation of the fluorescent moieties, observed in others approaches using encapsulation or conjugation of fluorescent molecules, additionally they show multi-stimuli response to temperature and pH. Both anionic (AFN) and cationic fluorescent nanogels (CFN) were successfully produced, which showed strong fluorescence intensity at neutral pH, the fluorescence was quenched at pH 5. Cisplatin (CDDP) and 5-fluorouracil (5-FU) were loaded into the nanogels, leading to partially quenching of the fluorescence. The kinetics of drug release and cell-viability studies are also reported. Cell-internalization studies were performed by fluorescence microscopy in non-small lung adenocarcinoma cell line NCI-H1437 and human colorectal cancer cell line HCT-116; demonstrating that the AFN were not internalized and CFN were easily internalized at concentrations of 100 µg/mL in 5 min, irrespective of the molecular weight of the Poly(ethylenglycol)-chains. The developed method can be expanded to the preparation of other fluorescent nanogel types; whereas the prepared AFN and CFN could be studied as nanocarriers to be internalized in diverse cell-lines.