组会讲课人员:李敏
Effective and Targeted Human Orthotopic Glioblastoma Xenograft Therapy via a Multifunctional Biomimetic Nanomedicine
通过多功能仿生纳米药物进行高效靶向的人类原位胶质母细胞瘤异种移植治疗
主讲人:李敏
Advanced Materials| December 2018 |Volume 30|Issue 51|1803717| https://doi.org/10.1002/adma.201803717
Abstract:
Glioblastoma multiforme (GBM) is a fatal central nervous system tumor without effective treatment. Chemotherapeutic agents are mainstays in the treatment of glioblastoma. However, the effectiveness of these is seriously hindered by poor blood–brain-barrier (BBB) penetrance and tumor targeting, together with short biological half-life. Improved chemotherapy is thus urgently needed for GBM. Multifunctional nanoparticle delivery systems offer much promise in overcoming current limitations. Accordingly, a multifunctional biomimetic nanomedicine is developed by functionalizing the surface of red blood cell membranes (RBCms) with angiopep-2 and loading pH-sensitive nanoparticles (polymer, doxorubicin (Dox), and lexiscan (Lex)) using the functionalized cell membrane to generate the novel nanomedicine, Ang-RBCm@NM-(Dox/Lex). The studies toward orthotopic U87MG human glioblastoma tumor-bearing nude mice show that the Ang-RBCm@NM-(Dox/Lex) nanomedicine has much improved blood circulation time, superb BBB penetration, superior tumor accumulation and retention. Moreover, effective suppression of tumor growth and significantly improved medium survival time are also observed after Ang-RBCm@NM-(Dox/Lex) treatment. The results show that this biomimetic nanoplatform can serve as a flexible and powerful system for GBM treatment which can be readily adapted for the treatment of other central nervous system (CNS) disorders.
摘要:
摘要:多形性胶质母细胞瘤(GBM)是一种致命的中枢神经系统肿瘤,没有有效的治疗方法。化疗药物是治疗胶质母细胞瘤的主要药物。然而,这些方法的有效性受到血脑屏障 (BBB) 穿透性和肿瘤靶向性差以及生物半衰期短的严重阻碍。因此,GBM 迫切需要改进的化学疗法。多功能纳米粒子递送系统在克服当前局限性方面提供了很大的希望。因此,一种多功能仿生纳米药物被开发了,通过用 angiopep-2 功能化红细胞膜 (RBCms) 的表面,并使用功能化的细胞膜负载 pH 敏感纳米粒子(聚合物、阿霉素 (Dox) 和 Lexiscan (Lex)),生成新型纳米药物Ang-RBCm@NM-(Dox/Lex)。对原位U87MG人胶质母细胞瘤荷瘤裸鼠的研究表明,Ang-RBCm@NM-(Dox/Lex)纳米药物具有显著改善的血液循环时间、极好的血脑屏障渗透、优越的肿瘤积累和保留。此外,在 Ang-RBCm@NM-(Dox/Lex) 处理后,还观察到有效抑制肿瘤生长和显著提高培养基存活时间。结果表明,这种仿生纳米平台可以作为一种灵活而强大的 GBM 治疗系统,可以很容易地适应其他中枢神经系统 (CNS) 疾病的治疗。