Pharmaceutical Research

, Volume 33, Issue 6, pp 1351–1358 | Cite as

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

  • M. Luísa Corvo
  • Ana Soraia Mendo
  • Sara Figueiredo
  • Rogério Gaspar
  • Miguel Larguinho
  • M. Fátima C. Guedes da Silva
  • Pedro Viana Baptista
  • Alexandra R Fernandes
Research Paper



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.


(targeted) long circulating liposomes antiproliferative colorectal carcinoma Sn(IV) complexes 







Distearoylphosphatidylethanolamine-poly(ethyleneglycol) 2000




Epidermal growth factor receptor


Colorectal carcinoma cells


Hepatocellular carcinoma cells


Inductively Coupled Plasma Mass Spectrometry


Empty Liposomes


[nBu2Sn(L)]3 (L=N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide)


MG85 incorporated in conventional/non-PEGylated liposomes


MG85 incorporated in Cetuximab targeted PEGylated liposomes labelled with Rho


Mononuclear phagocyte system


Polydispersity index


Polyethylene glycol


PEGylated liposomes labelled with Rho


Cetuximab targeted PEGylated liposomes labelled with Rho


phorbol 12-myristate-13 acetate


Rhodamine B


L-α-phosphoethanolamine-N-(lissamine Rhodamine B sulfonyl)


Human monocytic leukemia (THP1) cell line



We acknowledge Fundação para a Ciência e a Tecnologia (FCT/MEC) for financial support (Project PTDC/BBB-NAN/1812/2012; UCIBIO UID/Multi/04378/2013; UID/DTP/04138/2013). We thank M.Gajewska for MG85 synthesis and P. Borralho from iMed for Cetuximab.

M. Luísa Corvo and Ana Soraia Mendo contributed equally to the work.

Supplementary material

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Supplementary Figure S6

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • M. Luísa Corvo
    • 1
  • Ana Soraia Mendo
    • 2
  • Sara Figueiredo
    • 2
    • 3
  • Rogério Gaspar
    • 1
  • Miguel Larguinho
    • 2
  • M. Fátima C. Guedes da Silva
    • 4
  • Pedro Viana Baptista
    • 2
    • 3
  • Alexandra R Fernandes
    • 2
    • 4
  1. 1.Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de FarmáciaUniversidade de LisboaLisboaPortugal
  2. 2.UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e TecnologiaUniversidade NOVA de LisboaCaparicaPortugal
  3. 3.ToxOmics, Faculdade de Ciências MédicasUniversidade NOVA de LisboaLisboaPortugal
  4. 4.CQE, Centro de Química Estrutural, Instituto Superior TécnicoLisboaPortugal

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