文献:Manganese self-boosting hollow nanoenzymes with glutathione depletion for synergistic cancer chemo-chemodynamic therapy
文献链接:https://pubs.rsc.org/en/content/articlelanding/2024/bm/d4bm00386a/unauth
作者:Xinyi Cai , Deng Cai, Xiaozhen Wang , Dou Zhang , Long Qiu , Zhenying Diao , Yong Liu , Jianbo Sun, Daxiang Cui , Yanlei Liu , Ting Yin
相关产品:Cy5.5
原文摘要:
Chemodynamic therapy (CDT) has outstanding potential as a combination therapy to treat cancer. However, the effectiveness of CDT in the treatment of solid tumors is limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME). GSH overexpression diminishes oxidative stress and attenuates chemotherapeutic drug-induced apoptosis in cancer cells. To counter these effects, a synergistic CDT/chemotherapy cancer treatment, involving the use of a multifunctional bioreactor of hollow manganese dioxide (HMnO2) loaded with cisplatin (CDDP), was developed. Metal nanoenzymes that can auto-degrade to produce Mn2+ exhibit Fenton-like, GSH-peroxidase-like activity, which effectively depletes GSH in the TME to attenuate the tumor antioxidant capacity. In an acidic environment, Mn2+ catalyzed the decomposition of intra-tumor H2O2 into highly toxic ·OH as a CDT. HMnO2 with large pores, pore volume, and surface area exhibited a high CDDP loading capacity (>0.6 g−1). Treatment with CDDP-loaded HMnO2 increased the intratumor Pt-DNA content, leading to the up-regulation of γ-H2Aχ and an increase in tumor tissue damage. The decreased GSH triggered by HMnO2 auto-degradation protected Mn2+-generated ·OH from scavenging to amplify oxidative stress and enhance the efficacy of CDT. The nanoenzymes with encapsulated chemotherapeutic agents deplete GSH and remodel the TME. Thus, tumor CDT/chemotherapy combination therapy is an effective therapeutic strategy.
Cy5.5:Cy5.5 是一种花菁染料(Cyanine Dye),属于近红外荧光染料。它的化学结构包含共轭的多甲川链,这种结构是其产生荧光特性的关键。其最大吸收波长通常在 675 - 694nm 之间,最大发射波长约在 700 - 730nm 之间,具体的波长会因所处的化学环境等因素略有差异。由于其发射波长处于近红外区域,在生物医学等应用中有优势。与可见光波段的荧光染料相比,生物组织在近红外波段自身荧光较弱,对近红外光的吸收和散射也相对较少。这使得使用 Cy5.5 标记的生物样品在成像时,能够减少背景干扰,提高成像的对比度和分辨率,并且可以实现更深层次的组织穿透。基于Cy5.5的相关性能,介绍如下:
图:Cy5.5 结构式
生物反应器预处理:
若生物反应器需要清洗,记录清洗步骤。若有活化步骤,例如通过化学处理使表面产生特定官能团以便与 Cy5.5 结合,记录活化试剂、浓度、处理时间、温度等参数。
Cy5.5 标记:
根据需要标记的生物反应器数量与预期标记程度,计算并配制合适浓度的 Cy5.5 溶液。记录配制过程中所取的 Cy5.5 母液体积、稀释所用的缓冲溶液体积等信息。将预处理后的生物反应器与 Cy5.5 标记工作液混合。记录混合方式、混合比例、反应容器、反应温度与时间。在反应进行期间,定期取出少量反应混合液,使用荧光分光光度计检测 Cy5.5 的荧光强度变化,记录检测时间点与对应的荧光强度数据,以判断标记反应的进程。
图:机制示意
结论:
该文献成功制备出一种协同Treatment 方法---负载顺铂 (CDDP) 的空心二氧化锰 (HMnO 2 ) 多功能生物反应器。实验数据显示,这种多功能生物反应器取得了理想的预期结果。Cy5.5 在成像方面显示出良好的性能。