title: Liposomes as Delivery System of a Sn(IV) Complex for Cancer Therapy.
abstract: Tin complexes demonstrate antiproliferative activities in some case higher than cisplatin, with IC50 at the low micromolar range. We have previously showed that the cyclic trinuclear complex of Sn(IV) bearing an aromatic oximehydroxamic acid group [nBu2Sn(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.
  
  
  
  MG85 complex was encapsulated into liposomal formulation with and without an active targeting moiety and cancer and healthy cells cytotoxicity was evaluated.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: M Luísa
authors.initials: ML
authors.lastname: Corvo
authors.affiliation: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal.
authors.forename: Ana Soraia
authors.initials: AS
authors.lastname: Mendo
authors.affiliation: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal.|ToxOmics, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Rua Câmara Pestana, 1150-082, Lisboa, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Figueiredo
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Rogério
authors.initials: R
authors.lastname: Gaspar
authors.affiliation: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Larguinho
authors.affiliation: CQE, Centro de Química Estrutural, Instituto Superior Técnico, Av. Rovisco Pais, 1096-001, Lisboa, Portugal.
authors.forename: M Fátima C
authors.initials: MF
authors.lastname: Guedes da Silva
authors.affiliation: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal. pmvb@fct.unl.pt.|ToxOmics, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Rua Câmara Pestana, 1150-082, Lisboa, Portugal. pmvb@fct.unl.pt.
authors.forename: Pedro Viana
authors.initials: PV
authors.lastname: Baptista
authors.affiliation: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal. ma.fernandes@fct.unl.pt.|CQE, Centro de Química Estrutural, Instituto Superior Técnico, Av. Rovisco Pais, 1096-001, Lisboa, Portugal. ma.fernandes@fct.unl.pt.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Fernandes
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D001692:Biological Transport; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009947:Organotin Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D008081:Liposomes; D009947:Organotin Compounds; D011092:Polyethylene Glycols; D000068818:Cetuximab
keywords: (targeted) long circulating liposomes; Sn(IV) complexes; antiproliferative; colorectal carcinoma