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

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Abstract

Purpose

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.

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Abbreviations

ALG-CYS:

Alginate-cysteine conjugate

ANOVA:

One way analysis of variance

BSA:

Bovine serum albumin

BSA-SH:

Disulphide bond reduced bovine serum albumin

B-50-50 NP:

Nanoparticles based on 50% ALG-CYS and 50% BSA-SH

B-50-50-FOL NP:

Folate-conjugated nanoparticles based on 50% ALG-CYS and 50% BSA-SH

DCC:

N,N′-dicyclohexylcarbodiimide

DMSO:

Dimethyl sulphoxide

EDTA:

Ethylenediaminetetraacetic acid

FBS:

Foetal bovine serum

i.v:

Intravenous administration

KCl:

Potassium chloride

NaCl:

Sodium chloride

NaOH:

Sodium hydroxide

NP:

Nanoparticles

PBS:

Phosphate buffered saline

s.c:

Subcutaneous administration

TMX- B-50-50-FOL NP:

Tamoxifen-loaded folate-conjugated nanoparticles based on 50% ALG-CYS and 50% BSA-SH

TMX- B-50-50 NP:

Tamoxifen-loaded nanoparticles based on 50% ALG-CYS and 50% BSA-SH

4-OH-TMX:

4-hydroxytamoxifen

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Acknowledgments and Disclosures

The authors are grateful to Dr. von Kobbe (Chimera Pharma of Bionostra Group) for the gift of MCF7 cells. The financial support of the Ministerio de Ciencia e Innovación of Spain (FIS PS09/01513 and MAT2010-21509-C03-03), and the FPI grant from UCM to A. Martínez are also gratefully acknowledged.

Author information

Authors and Affiliations

  1. Departamento de Farmacología, Facultad de Farmacia Universidad Complutense de Madrid, Madrid, Spain

    A. Martínez & I. Iglesias

  2. Departamento de Biología Celular, Facultad de Biológicas Universidad Complutense de Madrid, Madrid, Spain

    E. Muñiz

  3. Departamento de Enfermería, Escuela Universitaria de Enfermería Fisioterapia y Podología, Universidad Complutense de Madrid, Madrid, Spain

    C. Teijón

  4. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain

    J. M. Teijón & M. D. Blanco

  5. Departamento de Bioquímica y Biología Molecular, Pabellón IV, Facultad de Medicina, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040, Madrid, Spain

    M. D. Blanco

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  1. A. Martínez
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  2. E. Muñiz
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  3. C. Teijón
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  4. I. Iglesias
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  6. M. D. Blanco
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Corresponding author

Correspondence to M. D. Blanco.

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Martínez, A., Muñiz, E., Teijón, C. et al. Targeting Tamoxifen to Breast Cancer Xenograft Tumours: Preclinical Efficacy of Folate-Attached Nanoparticles Based on Alginate-Cysteine/Disulphide-Bond-Reduced Albumin. Pharm Res 31, 1264–1274 (2014). https://doi.org/10.1007/s11095-013-1247-5

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  • DOI: https://doi.org/10.1007/s11095-013-1247-5

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