Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 623, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2022.121925
Keywords
Iron complexes; Malignant melanoma; Liposomes; In vivo studies; Anticancer; Phenanthrolines
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT) [UIDB/00100/2020, UIDP/00100/2020, UIDB/04138/2020, UIDP/04138/2020, PTDC/MED-QUI/31721/2017, PTDC/QUI-QIN/0586/2020, SFRH/BD/101214/2014, SFRH/BD/148044/2019]
- Fundação para a Ciência e a Tecnologia [PTDC/QUI-QIN/0586/2020, SFRH/BD/148044/2019, SFRH/BD/101214/2014] Funding Source: FCT
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Malignant melanoma, a deadly form of skin cancer, can potentially be treated using metallodrugs combined with liposomes for targeted delivery. In this study, a family of iron(III) complexes with high cytotoxic activity towards cancer cells was synthesized. One of the complexes was incorporated into a liposomal formulation, which demonstrated the highest impairment on tumor progression in vivo.
Malignant melanoma is an aggressive and deadly form of skin cancer and novel and improved therapeutic options are needed. A promising strategy involves the use of metallodrugs combined with liposomes for targeted delivery to cancer cells. In this work, a family of iron(III) complexes was synthesized bearing a trianionic aminobisphenolate ligand (L) and phenanthroline-type co-ligands (NN). Four ternary iron complexes of general formula [Fe(L)(NN)] were obtained: [Fe(L)(amphen)] (1), [Fe(L)(phen)] (2), [Fe(L)(Clphen)] (3), and [Fe(L) (Mephen)] (4), as well as a fifth complex [Fe(L)(NEt3)(H2O)] (5) without the bidentate co-ligand. All complexes were characterized by analytic and spectroscopic techniques and demonstrated to be stable in aqueous environment. Complexes 1 and 2 were able to bind DNA and presented high cytotoxic activity towards human cancer cells. Complex 1 (IronC) was selected for incorporation into different liposomal formulations, which were fully characterized and screened against murine melanoma cells. The IronC liposomal formulation with the highest incorporation efficiency (similar to 95%) and a low IC50 value (7.1 +/- 0.7 mu M) was selected for in vivo evaluation. In a syngeneic murine melanoma model the liposomal formulation of IronC yielded the highest impairment on tumour progression when compared with the control, temozolomide, and with the iron complex in free form.
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