Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities.
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.
Department of Hematology-Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Viviana P
VP
Montecinos
Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.|Hospital Clínico Dr. Félix Bulnes Cerda, Servicio de Salud Metropolitano Occidente, Santiago, Chile.
Claudio H
CH
Morales
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Thomas H
TH
Fischer
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
Sarah
S
Burns
Department of Urology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Ignacio F
IF
San Francisco
Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.|Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Alejandro S
AS
Godoy
Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Gary J
GJ
Smith
D000368:Aged; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D057005:Bioengineering / Q000379:methods*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005612:Freeze Drying; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D061848:Optical Imaging; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply*; D023041:Xenograft Model Antitumor Assays
D000728:Androgens
SPIO nanoparticles; androgen deprivation; human prostate xenografts; platelets