Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 213, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2022.112385
Keywords
Halloysite nanotubes; Methotrexate; Prodrug; Biotin; Drug delivery systems; Leukemia cells
Funding
- Andalusian Project [P18-RT-3786]
- Attrazione e Mobilit`a Internazionale [1808223-1]
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In this study, halloysite nanotubes (HNTs) loaded with methotrexate (MTX) and biotin ligand moieties were developed as multifunctional and smart delivery systems for targeted cancer therapy. The results showed that these systems exhibited promising cytotoxic effects on acute myeloid leukemia cell lines.
The prodrug approach, as well as the development of specific systems able to deliver a chemotherapeutic agent in the target site, decreasing the side effects often associated with its administration, are still a challenging. In this context, both methotrexate drug molecules (MTX) and biotin ligand moieties, whose receptors are overexpressed on the surface of several cancer cells, were loaded on halloysite nanotubes (HNTs) to develop nanomaterial based on multifunctional and smart delivery systems.To highlight the crucial role played by biotin, carrier systems based on HNTs and MTX were also synthetized. In detail, several approaches were envisaged: i) a supramolecular interaction between the clay and the drug; ii) a covalent grafting of the drug onto the HNTs external surface and, iii) a combination of both approaches. The nanomaterials obtained were characterized by thermogravimetric analysis, FT-IR, and UV-vis spectroscopies, DLS and zeta-potential measurements and the morphologies were imaged by HAADF/STEM investigations. Kinetic release experiments at different pH conditions were also performed. Finally, as a proof-of-concept application of our pro-drug delivery systems based on HNTs in cancer therapy, the cytotoxic effects were evaluated on acute myeloid leukemia cell lines, HL60 and its multidrug resistance variant, HL60R. The obtained results showed that both the MTX prodrug system and the biotinylated ones played a crucial role in the biological activity and, they are promising agents for the cancer treatments.
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