Targeting Tamoxifen to Breast Cancer Xenograft Tumours: Preclinical Efficacy of Folate-Attached Nanoparticles Based on Alginate-Cysteine/Disulphide-Bond-Reduced Albumin

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. 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. 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. 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.