研究动态
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多功能纳米雄黄水凝胶用于增强胶质母细胞瘤协同化疗和放疗:一个旧药物的新范式。

Multifunctional Nano-Realgar Hydrogel for Enhanced Glioblastoma Synergistic Chemotherapy and Radiotherapy: A New Paradigm of an Old Drug.

发表日期:2023
作者: Yihan Wang, Yizhen Wei, Yichun Wu, Yue Zong, Yingying Song, Shengyan Pu, Wenwen Wu, Yun Zhou, Jun Xie, Haitao Yin
来源: International Journal of Nanomedicine

摘要:

雄黄作为传统的矿物中药,在癌症治疗中可以抑制多种实体肿瘤的生长,成为一种辅助药物。然而,极低的溶解度和较差的体内吸收能力限制了它在临床医学上的应用。为了克服这一治疗难题,可以将雄黄制成纳米雄黄水凝胶,具有增强化疗和放疗能力。我们的目标是评估纳米雄黄水凝胶的优越生物相容性和抗肿瘤活性。我们成功地合成了与6-AN分子(NRA QDs)耦合的纳米雄黄量子点,并进一步封装在具有协同作用的pH敏感性的右旋糖基胶(BAX)和透明质酸涂层的载体所形成的多功能纳米雄黄水凝胶(NRA@DH Gel)中。为了更好地研究NRA@DH Gel的肿瘤治疗效率,我们建立了小鼠他们中GL261脑胶质母细胞瘤作为动物模型,注射NRA@DH Gel到肿瘤内。作为一种抗肿瘤药的设计的NRA@DH Gel不仅可以发挥突出的化疗作用,而且还可以作为“可持续产生反应性氧(RAS)的发生器”,并抑制五糖磷酸途径(PPP)代谢和减少烟酰胺腺嘌呤二核苷酸磷酸(NADPH)的产生,从而抑制谷胱甘肽二硫(GSSG)转化为谷胱甘肽(GSH)的过程,降低肿瘤细胞中GSH浓度,促进ROS的积累,最终增强放疗的有效性。通过化疗和放疗的协同作用,NRA@DH Gel有效抑制了肿瘤细胞的增殖和迁移,抑制了肿瘤生长,改善了运动协调性,并延长了带瘤小鼠的存活期。我们的工作旨在通过增强NRA@DH Gel介导的协同化疗和放疗,使其在临床上获得“光明的未来”。©2023 Wang等。
Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel.We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel.The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a "sustainable reactive oxygen species (ROS) generator" can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT.Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a "promising future" for the old drug in clinically comprehensive applications.© 2023 Wang et al.