Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 19, Issue 7, Pages 1530-1537Publisher
WILEY
DOI: 10.1111/jcmm.12515
Keywords
platelets; androgen deprivation; human prostate xenografts; SPIO nanoparticles
Categories
Funding
- National Institutes of Health [PO1-CA-77739]
- Department of Defense [W81XWH-08-1-0299, W81XWH-08-1-0330, W81XWH-04-1-0264]
- FONDEF grant, Chile [CA12i1033]
- National Cancer Institute Cancer Center Support Grant [CA-016156]
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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.
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