DOI: https://doi.org/10.29363/nanoge.amamed.2022.013
Publication date: 22nd April 2022
Cancer metastasis is a complex process in which cells break out the primary tumor mass by invading and colonizing a new site. When patients are diagnosed with metastatic cancer, such as colorectal cancer (CRC), metastasis has already spread to another part of the body and conventional therapies fail to target cancer cells. The transforming growth factor-β inhibitor Galunisertib has been recently approved for the treatment of metastatic CRC due to its ability to revert the metastatic process and induce cell epithelization. However, the oral administration of Galunisertib causes systemic toxicity and side effects. The controlled delivery of Galunisertib to CRC through nanoparticle-based approaches can be a valid weapon to increase the drug concentration at the tumor site and improve the therapy outcomes. To this aim, porous diatomite nanoparticles (DNPs) were loaded with Galunisertib and capped with gelatin to provide the nanocarrier with pH-responsive properties. In this study, the tumor acidic microenvironment triggered the release of Galunisertib from DNPs in a sustained and selective manner. The gelatin-capped platform showed a pH and time-dependent release profile provided by the presence of gelatin. Indeed, gelatin remains folded in physiological conditions, hampering the release of Galunisertib from the nanosystem, whereas the acidic environment promoted the drug release. Here, for the first time, the drug release was monitored in living CRC cells via Surface-Enhanced Raman Scattering. The surface of DNPs was decorated with gold nanoparticles that enhanced the Raman signal of the loaded drug and enabled to trace the Galunisertib delivery from the nanocarrier to cells down to femtogram scales. Finally, in vitro studies performed on the CRC cell line confirmed that the controlled delivery of Galunisertib from modified-DNPs induced the cell epithelization more efficiently than the free drug.
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