Open AccessSelective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities
Author(s) -
Montecinos Viviana P.,
Morales Claudio H.,
Fischer Thomas H.,
Burns Sarah,
San Francisco Ignacio F.,
Godoy Alejandro S.,
Smith Gary J.
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12515
Subject(s) - prostate cancer , medicine , cancer research , prostate , platelet , androgen deprivation therapy , cancer
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.