Intracellular SERS monitoring of drug release from plasmonic-assisted biosilica nanoparticles

Nanoscale delivery systems have been investigated for therapy due to their advantages, including the sustained delivery of drugs to cells and reduction of systemic toxicity compared to conventional treatments. However, their application is still hampered by experimental challenges, such as the investigation of the drug release in cells rather than in vitro . Here, we describe a hybrid nanoplatform for monitoring the drug release in living colorectal cancer (CRC) cells by Surface-Enhanced Raman Scattering (SERS). Specifically, the anticancer drug Galunisertib is encapsulated in diatomite nanoparticles (DNPs) decorated by gold nanoparticles (AuNPs) and capped by gelatin. The combination of DNP loading capacities with the Raman enhancement of Galunisertib provided by AuNPs enables bio-imaging and drug delivery without using fluorophores or markers, avoiding fluorescence-quenching issues. Thanks to the Raman enhancement of Galunisertib, the drug release profile is monitored and quantified in living cells by SERS with a femtogram scale resolution. When the gelatin shell is digested by proteases, Galunisertib is released and its SERS spectrum decreases, allowing real-time quantification in CRC cells. The therapeutic efficiency of the Galunisertib delivery platform offers an alternative route for lowering drug dose and toxicity.