Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities

Journal of Cellular and Molecular Medicine

Viviana P. Montecinos²  Claudio H. Morales⁵  Thomas H. Fischer³  Sarah Burns¹  Ignacio F. San Francisco⁴  Alejandro S. Godoy⁵ 

[1] Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA;Department of Hematology-Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile;Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Department of Urology, Pontificia Universidad Católica de Chile, Santiago, Chile;Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA

关键词: platelets;    androgen deprivation;    human prostate xenografts;    SPIO nanoparticles;   

DOI  :  10.1111/jcmm.12515

来源: Wiley

【 摘 要 】

Abstract

Androgen deprivation therapy (ADT) provides palliation for most patients with advanced prostate cancer (CaP); however, greater than 80% subsequently fail ADT. ADT has been indicated to induce an acute but transient destabilization of the prostate vasculature in animal models and humans. Human re-hydrated lyophilized platelets (hRL-P) were investigated as a prototype for therapeutic agents designed to target selectively the tumour-associated vasculature in CaP. The ability of hRL-P to bind the perturbed endothelial cells was tested using thrombin- and ADP-activated human umbilical vein endothelial cells (HUVEC), as well as primary xenografts of human prostate tissue undergoing acute vascular involution in response to ADT. hRL-P adhered to activated HUVEC in a dose-responsive manner. Systemically administered hRL-P, and hRL-P loaded with super-paramagnetic iron oxide (SPIO) nanoparticles, selectively targeted the ADT-damaged human microvasculature in primary xenografts of human prostate tissue. This study demonstrated that hRL-P pre-loaded with chemo-therapeutics or nanoparticles could provide a new paradigm for therapeutic modalities to prevent the rebound/increase in prostate vasculature after ADT, inhibiting the transition to castration-recurrent growth.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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