Design, Synthesis, Characterization, and Evaluation of the Anti-HT-29 Colorectal Cell Line Activity of Novel 8-Oxyquinolinate-Platinum(II)-Loaded Nanostructured Lipid Carriers Targeted with Riboflavin
Tugce Boztepe,
Sebastián Scioli-Montoto,
Rocio C. Gambaro,
María Esperanza Ruiz,
Silvia Cabrera,
José Alemán,
Germán A. Islan,
Guillermo R. Castro,
Ignacio E. León
Affiliations
Tugce Boztepe
Laboratorio de Nanobiomateriales, CINDEFI—Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET, La Plata B1900, Argentina
Sebastián Scioli-Montoto
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata B1904, Argentina
Rocio C. Gambaro
Instituto de Genética Veterinaria (IGEVET, UNLP-CONICET La Plata), Facultad de Ciencias Veterinarias Universidad Nacional de La Plata (UNLP), La Plata B1900, Argentina
María Esperanza Ruiz
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata B1904, Argentina
Silvia Cabrera
Departamento de Química Inorgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain
José Alemán
Departamento de Química Orgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain
Germán A. Islan
Laboratorio de Nanobiomateriales, CINDEFI—Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET, La Plata B1900, Argentina
Guillermo R. Castro
Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC), Partner Laboratory of the Max Planck Institute for Biophysical Chemistry (MPIbpC, MPG), Centro de Estudios Interdisciplinarios (CEI), Universidad Nacional de Rosario, Rosario S2000, Argentina
Ignacio E. León
CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata B1900, Argentina
Colorectal cancer is occasionally called colon or rectal cancer, depending on where cancer begins to form, and is the second leading cause of cancer death among both men and women. The platinum-based [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) compound has demonstrated encouraging anticancer activity. Three different systems of 8-QO-Pt-encapsulated nanostructured lipid carriers (NLCs) with riboflavin (RFV) were investigated. NLCs of myristyl myristate were synthesized by ultrasonication in the presence of RFV. RFV-decorated nanoparticles displayed a spherical shape and a narrow size dispersion in the range of 144–175 nm mean particle diameter. The 8-QO-Pt-loaded formulations of NLC/RFV with more than 70% encapsulation efficiency showed sustained in vitro release for 24 h. Cytotoxicity, cell uptake, and apoptosis were evaluated in the HT-29 human colorectal adenocarcinoma cell line. The results revealed that 8-QO-Pt-loaded formulations of NLC/RFV showed higher cytotoxicity than the free 8-QO-Pt compound at 5.0 µM. All three systems exhibited different levels of cellular internalization. Moreover, the hemotoxicity assay showed the safety profile of the formulations (less than 3.7%). Taken together, RFV-targeted NLC systems for drug delivery have been investigated for the first time in our study and the results are promising for the future of chemotherapy in colon cancer treatment.
