Abstract

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.

Highlights

  • The research for nanoscale Drug Delivery Systems (DDS) is driven by their potentiality to reduce the systemic toxicity associated with small-molecule administration

  • The presence of AuNPs was confirmed by Transmission Electron Microscopy (TEM) investigation (Fig. 2A), showing that the surface of diatomite nanoparticles (DNPs) was covered by a homogeneous carpet of AuNPs after the synthesis process

  • The presence of metal NPs on the silica structure conferred to the DNPs a localized surface plasmon resonance (LSPR) at 576 nm wavelength, which enabled monitoring the functionalization via absorbance analysis (UV-Visible spectroscopy)

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Summary

Introduction

The research for nanoscale Drug Delivery Systems (DDS) is driven by their potentiality to reduce the systemic toxicity associated with small-molecule administration. The plasmonic and electromagnetic properties of gold NPs (AuNPs) offer high-sensitivity and Raman enhancement factors up to 1012 for absorbed or attached molecules on metal surfaces or NPs. the combination of the strong Raman enhancement of molecules provided by AuNPs with the loading capacity of porous NPs can be used to develop hybrid platforms capable of both delivering and real-time quantifying the released drug in cells [3].

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