Xingshu Li, Jae Sang Oh, Yoonji Lee, Eun Chae Lee, Mengyao Yang, Nahyun Kwon, Tae Won Ha, Dong-Yong Hong, Yena Song, Hyun Kyu Kim, Byung Hoo Song, Sun Choi, Man Ryul Lee, Juyoung Yoon
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引用次数: 1
摘要
背景:恶性胶质瘤是脑肿瘤中最常见、最致命的肿瘤之一，平均生存期为15个月。现有化疗药物耐受性低，血脑屏障(BBB)通透性低;因此，所需的药物剂量不能准确地传递到肿瘤部位，导致药物效果不足。方法:在此，我们展示了一种精确的光动力肿瘤治疗方法，使用一种能够与白蛋白原位结合的光敏剂(ZnPcS)，它可以增加血脑屏障的通透性并准确靶向胶质瘤。白蛋白结合型锌细胞通过血脑屏障，与分泌的富含半胱氨酸(SPARC)的酸性蛋白结合，而SPARC在胶质瘤质膜中含量丰富。结果:胶质瘤移植后，用激光(0.2 W cm- 2)照射小鼠脑上半部分并注射ZnPcS，肿瘤生长被抑制约83.6%，治疗组50%存活率较对照组提高14天。在敲除SPARC的胶质瘤中，ZnPcS进入胶质瘤的数量减少了63.1%，表明它可以通过SPARC途径靶向胶质瘤。结论:白蛋白结合光敏剂在恶性胶质瘤的治疗中具有广阔的应用前景。
Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway.
Background: Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect.
Methods: Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane.
Results: When the upper part of a mouse brain was irradiated using a laser (0.2 W cm- 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway.
Conclusion: This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas.
期刊介绍：
Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.
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