Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, Buffalo, NY, USA.
Nanomedicine. 2022 Apr;41:102513. doi: 10.1016/j.nano.2021.102513. Epub 2021 Dec 24.
Current glioblastoma multiforme (GBM) treatment is insufficient, facing obstacles like poor tumor accumulation and dose limiting side effects of chemotherapeutic agents. Targeted nanomaterials offer breakthrough potential in GBM treatment; however, traditional antibody-based targeting poses challenges for live brain application. To overcome current obstacles, we introduce here the development of a small molecule targeting agent, CFMQ, coupled to biocompatible chitosan coated poly(lactic-co-glycolic) acid nanoparticles. These targeted nanoparticles enhance cellular uptake and show rapid blood-brain barrier (BBB) permeability in-vitro, demonstrating the ability to effectively deliver their load to tumor cells. Encapsulation of the chemotherapeutic agent, temozolomide (TMZ), decreases the IC ~34-fold compared to free-drug. Also, CFMQ synergistically suppresses tumor cell progression, reducing colony formation (98%), cell migration (84%), and cell invasion (77%). Co-encapsulation of Cy5 enables optical image guided therapy. This biocompatible theranostic nanoformulation shows early promise in significantly enhancing the efficacy of TMZ, while providing potential for image-guided therapy for GBM.
目前胶质母细胞瘤（GBM）的治疗方法效果不佳，面临着诸如肿瘤蓄积不良和化疗药物剂量限制的副作用等障碍。靶向纳米材料为 GBM 的治疗提供了突破的潜力；然而，传统的基于抗体的靶向方法在活体脑应用中存在挑战。为了克服当前的障碍，我们在这里介绍了一种小分子靶向剂 CFMQ 与生物相容性壳聚糖包覆的聚（乳酸-共-乙醇酸）纳米粒子的结合。这些靶向纳米粒子增强了细胞摄取，并表现出快速的血脑屏障（BBB）渗透性，能够有效地将其载药递送到肿瘤细胞。与游离药物相比，化疗药物替莫唑胺（TMZ）的包封使 IC 降低了 34 倍。此外，CFMQ 协同抑制肿瘤细胞的进展，降低集落形成（98%）、细胞迁移（84%）和细胞侵袭（77%）。Cy5 的共包封实现了光学图像引导治疗。这种生物相容性的治疗纳米制剂在显著增强 TMZ 的疗效方面显示出早期的前景，同时为 GBM 的图像引导治疗提供了潜力。
