Targeting tamoxifen to breast cancer xenograft tumours: preclinical efficacy of folate-attached nanoparticles based on alginate-cysteine/disulphide-bond-reduced albumin.
OBJECTIVE
In vivo evaluation of tamoxifen (TMX)-loaded folate-targeted nanoparticles prepared from a mixture of disulphide bond reduced bovine serum albumin (BSA-SH) and alginate-cysteine (ALG-CYS) as targeted delivery systems of TMX to tumour tissues.


METHODS
TMX in solution, TMX included into folate-nanoparticles and their non-targeted analogues were intravenously administered to nude mice carrying xenograft MCF-7 tumours. The antitumor activity of these systems was characterized in terms of tumour growth rate, histological and immunohistochemical analysis of tumour tissues and TMX biodistribution.


RESULTS
TMX-folate-attached nanoparticles caused tumour remission whereas free TMX or TMX-non-targeted nanoparticles could only stop the tumour development. The histological evaluation of tumour tissues showed that those treated with folate-conjugated systems presented the most quiescent and disorganized structures. Additionally, the lowest concentrations of TMX accumulated in non-targeted organs were also found after administration of the drug using this formulation.


CONCLUSIONS
This study demonstrated that TMX-loaded folate-targeted systems were capable of reaching tumour sites, so enhancing the in vivo anticancer action of TMX, and allowing a new administration route to be applied and some of the current TMX therapy problems to be overcome.
Departamento de Farmacología, Facultad de Farmacia Universidad Complutense de Madrid, Madrid, Spain.
A
A
Martínez
E
E
Muñiz
C
C
Teijón
I
I
Iglesias
J M
JM
Teijón
M D
MD
Blanco
D000418:Albumins / Q000737:chemistry; D000464:Alginates / Q000737:chemistry; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D000418:Albumins; D000464:Alginates; D004220:Disulfides; D006603:Hexuronic Acids; D013629:Tamoxifen; D020723:Glucuronic Acid; D005492:Folic Acid; D003545:Cysteine