Effect of Retro-Inverso Isomer of Bradykinin on Size-Dependent Penetration of Blood–Brain Tumor Barrier
Effect of Retro-Inverso Isomer of Bradykinin on Size-Dependent Penetration of Blood–Brain Tumor Barrier
复制标题
缓激肽逆向异构体对血脑肿瘤屏障尺寸依赖性穿透的影响
作者：
苏冰霞;王睿峰;谢作旭;阮惠瞳;李济忱;谢操;陆伟跃;王晶;王董理;刘敏
与缓激肽相比，反向缓激肽（RI-BK）具有更好的代谢稳定性和对BK 2型（B2）受体更高的亲和力。在低剂量下，RI-BK可以选择性地增强血脑肿瘤屏障（BBTB）的通透性，而不会损害正常脑组织。在这项研究中，合成了尺寸范围为5至90 nm的金纳米颗粒（GNP），以评估RI-BK治疗后实现最大脑蓄积的纳米载体的最佳尺寸。在大鼠C6神经胶质瘤肿瘤模型中测试了GNP穿过BBTB的能力。电感耦合等离子体质谱和透射电子显微镜的结果表明，GNP的大小为70 nm达到最大的渗透性胶质瘤。本研究支持了RI-BK可以增强BBTB的通透性的结论，并为进一步开发用于胶质瘤治疗的纳米药物或纳米探针提供了基础信息。
Retro-inverso bradykinin (RI-BK) has better metabolic stability and higher affinity for the BK type 2 (B2) receptor, compared with bradykinin. At low doses, RI-BK can selectively enhance the permeability of the blood–brain tumor barrier (BBTB) without harming normal brain tissue. In this study, gold nanoparticles (GNPs) of size ranging from 5 to 90 nm are synthesized to assess the optimal size of nanocarriers that achieves maximum brain accumulation after the treatment of RI-BK. The ability of the GNPs to cross the BBTB is tested in a rat C6 glioma tumor model. The results of inductively coupled plasma–mass spectrometry and transmission electron microscopy indicate that GNPs with size of 70 nm achieve maximum permeability to the glioma. The present study supports the conclusion that RI-BK can enhance the permeability of BBTB and provides fundamental information for further development of nanomedicines or nanoprobes for glioma therapy.