Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities.
Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities.
复制标题
生物工程血小板选择性靶向前列腺癌脉管系统：治疗方式的新范例。
DOI：
10.1111/jcmm.12515
复制
发表时间：
2015
影响因子：
5.3
通讯作者：
Smith,GaryJ
中科院分区：
文献类型：
--
作者：
Montecinos,VivianaP;Morales,ClaudioH;Fischer,ThomasH;Burns,Sarah;SanFrancisco,IgnacioF;Godoy,AlejandroS;Smith,GaryJ
雄激素剥夺疗法（ADT）为大多数晚期前列腺癌（CaP）患者提供了缓解；然而，超过80%的患者随后ADT失败。在动物模型和人类中，ADT已被证明可诱导急性但短暂的前列腺血管不稳定。人类再水合冻干血小板（hRL‐P）作为治疗药物的原型，被设计用于选择性靶向CaP中的肿瘤相关血管。hRL‐P结合受干扰的内皮细胞的能力通过凝血酶和ADP激活的人脐静脉内皮细胞（HUVEC）以及ADT引起的急性血管内陷的人前列腺组织的原发异种移植物进行了测试。hRL‐P以剂量反应的方式粘附在活化的HUVEC上。系统给药hRL - P和装载超顺磁性氧化铁（SPIO）纳米颗粒的hRL - P选择性靶向ADT损伤的人类微血管，用于原发性异种前列腺组织移植。该研究表明，hRL - P预载化疗药物或纳米颗粒可以提供一种新的治疗模式，以防止ADT后前列腺血管的反弹/增加，抑制向去势复发生长的过渡。
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.