Mechanisms of tumor vascular priming by a nanoparticulate doxorubicin formulation.
Mechanisms of tumor vascular priming by a nanoparticulate doxorubicin formulation.
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DOI：
10.1007/s11095-012-0823-4
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发表时间：
2012-12
影响因子：
3.7
通讯作者：
Straubinger, Robert M.
中科院分区：
文献类型：
--
作者：
Chaudhuri, Tista Roy;Arnold, Robert D.;Yang, Jun;Turowski, Steven G.;Qu, Yang;Spernyak, Joseph A.;Mazurchuk, Richard;Mager, Donald E.;Straubinger, Robert M.
关键词：
抗血管生成药物使肿瘤血管正常化可增加肿瘤的血流灌注，但重建中枢神经系统肿瘤的血管屏障特性。通过纳米颗粒载体进行血管预充是一种机械上截然不同的替代方法。这项研究探讨了空间稳定的脂质体阿霉素(SSLDXR)调节肿瘤血管特性的机制。应用荧光渗透性探针沉积和动态增强磁共振成像技术，研究了SSLDXR对大鼠原位脑肿瘤的功能性血管反应。采用免疫组织化学方法(CD-31)和定量逆转录聚合酶链式反应(VE-cadherin)检测肿瘤微血管密度和肿瘤负荷。静脉注射SSLDXR(5.7 mg/kg)可降低肿瘤血管通透性、血管交换常数、血管内皮细胞含量、微血管密度和纳米颗粒沉积。肿瘤血管变得不那么混乱了。治疗后6-7天，肿瘤的通透性和灌注量恢复到对照组水平，但瘤内的SSL-DXR储存库在治疗后7-10天继续影响肿瘤血管内皮细胞，介导通透性增强。SSLDXR最终增加了肿瘤血管的渗透性，但最初使肿瘤血管正常化，降低了肿瘤的灌注量、渗透率和纳米颗粒的沉积。这些由单次SSLDXR剂量引起的血管完整性的时间变化对于设计结合纳米颗粒为基础的药物用于肿瘤血管启动具有重要的意义。
Tumor vascular normalization by antiangiogenic agents may increase tumor perfusion but reestablish vascular barrier properties in CNS tumors. Vascular priming via nanoparticulate carriers represents a mechanistically distinct alternative. This study investigated mechanisms by which sterically-stabilized liposomal doxorubicin (SSL-DXR) modulates tumor vascular properties. Functional vascular responses to SSL-DXR were investigated in orthotopic rat brain tumors using deposition of fluorescent permeability probes and dynamic contrast-enhanced magnetic resonance imaging. Microvessel density and tumor burden were quantified by immunohistochemistry (CD-31) and quantitative RT-PCR (VE-cadherin). Administration of SSL-DXR (5.7 mg/kg iv) initially (3–4 days post-treatment) decreased tumor vascular permeability, ktrans (vascular exchange constant), vascular endothelial cell content, microvessel density, and deposition of nanoparticulates. Tumor vasculature became less chaotic. Permeability and perfusion returned to control values 6–7 days post-treatment, but intratumor SSL-DXR depot continued to effect tumor vascular endothelial compartment 7–10 days post-treatment, mediating enhanced permeability. SSL-DXR ultimately increased tumor vascular permeability, but initially normalized tumor vasculature and decreased tumor perfusion, permeability, and nanoparticulate deposition. These temporal changes in vascular integrity resulting from a single SSL-DXR dose have important implications for the design of combination therapies incorporating nanoparticle-based agents for tumor vascular priming.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
5.2
作者：
Ghods, Ali Jourabcih;Irvin, Dwain;Yu, John S.
通讯作者：
Yu, John S.
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
DOI：
10.1073/pnas.85.18.6949
发表时间：
1988-09-01
影响因子：
11.1
作者：
GABIZON, A;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
影响因子：
2.6
作者：
JAIN, RK
通讯作者：
JAIN, RK