Ag nanocubes/cationic cellulose nanofibers/polyacrylamide hydrogel as a SERS platform for in situ separation, rapid enrichment and sensitive detection of anticancer drugs in plasma

Surface Enhanced Raman Spectroscopy (SERS) is always challenging for the detection of complex samples due to the pre-processing issues. Therefore, there is a need to develop a high-performance SERS platform that can avoid pre-processing problems and simultaneously enrich target molecules. In this work, we encapsulated cationic cellulose nanofibers (CCNF) stabilized Ag NCs in polyacrylamide hydrogels via photo-crosslinking to construct a high-performance SERS platform for rapid separation, concentration, and enrichment without pretreatment. Ag NCs/CCNF/PAAM hydrogels have good swelling and shrinking properties, which are favorable for enriching the substances to be measured and improving the sensitivity of the SERS platform. The limit of detection (LOD) was as low as 9.33 × 10−11 M for the detection of the dye molecule R6G. The hydrogel SERS platform has excellent selectivity. Its pores can be adjusted to allow the entry of small hydrophilic molecules and the exclusion of large molecules and hydrophobic substances in complex samples. Therefore, we performed the SERS assay for hydrophilic anticancer drugs in the plasma environment, where the hydrogel allowed doxorubicin hydrochloride (DOX) and 6-thioguanine (6-TG) to enter into the interior of the hydrogel, while hydrophobic substances such as plasma proteins and lipids in plasma were excluded from the hydrogel. As a validation, we performed spiking experiments on plasma from five lung cancer patients, and the assay was sensitive and reliable, with recoveries ranging from 89.0% to 111.0%. Based on the above results, Ag NCs/CCNF/PAAM hydrogels are promising for the real-time detection of drugs in clinical blood.