Anti-Invasive Peptide-Functionalized Nanotubes for Selective c‑Met Targeting and Metal Chelation

This work describes the development of a sustainable and biocompatible drug delivery system using halloysite nanotubes (HNTs). The goal was to create a material that could both deliver the chemotherapy drug doxorubicin (DOX) and selectively target the tumor cells. The synthesis process was made environmentally friendly by using tetrahydropyran (Thp) as a solvent. The HNTs were first functionalized with an amino group using (3-aminopropyl)-triethoxysilane (APTES), followed by the conjugation of two different peptides, P1 and P2, via EDC coupling. Successful functionalization was confirmed by FTIR spectroscopy, and through thermogravimetric analysis (TGA), we determined the degree of functionalization (%f). The DOX loading efficiency was found to be 8.8% for all composites, indicating that the peptides did not interfere with drug loading. Drug release studies showed that HNT-NH-P1 exhibited a faster release rate, releasing 9% of DOX in 24 h, while HNT-NH-P2 showed a much slower release of only 3.5% over the same period. Furthermore, in vitro scratch assays revealed a selective antimigratory effect of HNT-NH-P1-DOX on c-Met-positive adenocarcinoma cells, suggesting a receptor-mediated targeting potential. Finally, as a feasibility proof-of-concept for potential radiopharmaceutical applications, the HNT-NH-P1 platform was successfully extended with a THP chelator, demonstrating a high coordination capacity for trivalent Ga. These results demonstrate the potential of HNTs as versatile platforms for targeted drug delivery and imaging applications.