Li Xingyue, Ta Wenjing, Hua Ruochen, Song Jihong, Lu Wen
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an 710061, China.
Biomedicines. 2022 Oct 1;10(10):2455. doi: 10.3390/biomedicines10102455.
Glioma is an invasive brain cancer, and it is difficult to achieve desired therapeutic effects due to the high postoperative recurrence rate and limited efficacy of drug therapy hindered by the biological barrier of brain tissue. Nanodrug delivery systems are of great interest, and many efforts have been made to utilize them for glioma treatment. Polyamidoamine (PAMAM), a starburst dendrimer, provides malleable molecular size, functionalized molecular structure and penetrable brain barrier characteristics. Therefore, PAMAM-based nanodrug delivery systems (PAMAM DDS) are preferred for glioma treatment research. In this review, experimental studies on PAMAM DDS for glioma therapy were focused on and summarized. Emphasis was given to three major topics: methods of drug loading, linkers between drug/ligand and PAMAM and ligands of modified PAMAM. A strategy for well-designed PAMAM DDS for glioma treatment was proposed. Purposefully understanding the physicochemical and structural characteristics of drugs is necessary for selecting drug loading methods and achieving high drug loading capacity. Additionally, functional ligands contribute to achieving the brain targeting, brain penetration and low toxicity of PAMAM DDS. Furthermore, a brilliant linker facilitates multidrug combination and multifunctional PAMAM DDS. PAMAM DDS show excellent promise as drug vehicles and will be further studied for product development and safety evaluation.
胶质瘤是一种侵袭性脑癌，由于术后复发率高以及药物治疗效果受脑组织生物屏障限制而疗效有限，难以达到理想的治疗效果。纳米药物递送系统备受关注，人们已做出诸多努力将其用于胶质瘤治疗。聚酰胺 - 胺（PAMAM），一种树枝状大分子，具有可调节的分子大小、功能化的分子结构以及可穿透血脑屏障的特性。因此，基于PAMAM的纳米药物递送系统（PAMAM DDS）成为胶质瘤治疗研究的首选。在本综述中，重点关注并总结了关于PAMAM DDS用于胶质瘤治疗的实验研究。着重探讨了三个主要主题：药物负载方法、药物/配体与PAMAM之间的连接子以及修饰PAMAM的配体。提出了一种用于胶质瘤治疗的精心设计的PAMAM DDS策略。有目的地了解药物的物理化学和结构特性对于选择药物负载方法和实现高药物负载量至关重要。此外，功能性配体有助于实现PAMAM DDS的脑靶向、脑穿透以及低毒性。再者，出色的连接子有利于多药联合和多功能PAMAM DDS的构建。PAMAM DDS作为药物载体展现出极佳的前景，将进一步开展产品研发和安全性评估研究。
