Liposomes as Delivery System of a Sn(IV) Complex for Cancer Therapy

• Published in: Pharmaceutical research 2016-06, Vol.33 (6), p.1351-1358
• Main Authors: Corvo, M. Luísa, Mendo, Ana Soraia, Figueiredo, Sara, Gaspar, Rogério, Larguinho, Miguel, Guedes da Silva, M. Fátima C., Baptista, Pedro Viana, Fernandes, Alexandra R
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - toxicity; Apoptosis; Biochemistry; Biological Transport; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer; Cancer therapies; Care and treatment; Cell Proliferation - drug effects; Cell Survival - drug effects; Cellular biology; Cetuximab - administration & dosage; Cetuximab - chemistry; Cetuximab - metabolism; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Dose-Response Relationship, Drug; Drug Compounding; Drug Delivery Systems - methods; HCT116 Cells; Health aspects; Hep G2 Cells; Humans; Inhibitory Concentration 50; Kinetics; Lipids - chemistry; Liposomes; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Medical Law; Metals; Organotin Compounds - administration & dosage; Organotin Compounds - chemistry; Organotin Compounds - metabolism; Organotin Compounds - toxicity; Pharmacology/Toxicology; Pharmacy; Polyethylene Glycols - chemistry; Research Paper; Tubulins
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-016-1876-6

ABSTRACT Propose Tin complexes demonstrate antiproliferative activities in some case higher than cisplatin, with IC 50 at the low micromolar range. We have previously showed that the cyclic trinuclear complex of Sn(IV) bearing an aromatic oximehydroxamic acid group [nBu 2 Sn(L)] 3 (L= N ,2-dihydroxy-5-[ N -hydroxyethanimidoyl]benzamide) (MG85) shows high anti-proliferative activity, induces apoptosis and oxidative stress, and causes destabilization of tubulin microtubules, particularly in colorectal carcinoma cells. Despite the great efficacy towards cancer cells, this complex still shows some cytotoxicity to healthy cells. Targeted delivery of this complex specifically towards cancer cells might foster cancer treatment. Methods MG85 complex was encapsulated into liposomal formulation with and without an active targeting moiety and cancer and healthy cells cytotoxicity was evaluated. Results Encapsulation of MG85 complex in targeting PEGylated liposomes enhanced colorectal carcinoma (HCT116) cancer cell death when compared to free complex, whilst decreasing cytotoxicity in non-tumor cells. Labeling of liposomes with Rhodamine allowed assessing internalization in cells, which showed significant cell uptake after 6 h of incubation. Cetuximab was used as targeting moiety in the PEGylated liposomes that displayed higher internalization rate in HCT116 cells when compared with non-targeted liposomes, which seems to internalize via active binding of Cetuximab to cells. Conclusions The proposed formulation open new avenues in the design of innovative transition metal-based vectorization systems that may be further extended to other novel metal complexes towards the improvement of their anti-cancer efficacy, which is usually hampered by solubility issues and/or toxicity to healthy tissues.