一种基于共价有机框架的多功能治疗平台通过催化级联反应增强光动力治疗

A covalent organic framework-based multifunctional therapeutic platform for enhanced photodynamic therapy via catalytic cascade reactions

近年来,利用肿瘤独特的微环境进行肿瘤治疗成为了热门研究话题,然而这种治疗方法经常受到诸多条件的限制,如较少的反应底物和较慢的反应速率,反应所产生的毒性物质也不足以杀死癌细胞等.本文以共价有机骨架(COFs)为模板,在表面生长金纳米颗粒,然后再包覆一层二氧化锰,最后用透明质酸修饰以提高材料的生物相容性.最终得到的产物可以在肿瘤微环境中形成级联反应:在缺氧条件下,二氧化锰可以分解肿瘤内部的过氧化氢产生氧气以增强II型光动力疗法;金纳米颗粒可以通过分解葡萄糖用于饥饿疗法,同时,饥饿疗法所产生的过氧化氢又可以促进氧气的生成.此外,肿瘤内部的谷胱甘肽可以将二氧化锰分解为二价锰离子,而二价锰离子可以用于T1加权MR成像.最终体内和体外实验证明,该复合材料具有良好的癌细胞杀伤能力和抗肿瘤效果.

Utilizing the unique tumor microenvironment(TME)to conduct chemical reactions for cancer treatment becomes a hot topic recently.Nevertheless,single chemical reaction in TME is often restricted by scanty reaction substrates and slow reaction rate.Meanwhile,the toxic substances produced by the reactions are usually not enough to kill cancer cells.Herein,using covalent organic frameworks(COFs)as the template,Au nanoparticles(Au NPs)were subsequently grown on the surface of the COF,then a thin layer of manganese dioxide(MnO2)was coated over the material,and finally hyaluronic acid(HA)was introduced to improve the biocompatibility.The resultant product,named COF-Au-MnO2,was involved in several processes to form cascade reactions in the TME.Specifically,under hypoxic conditions,COF-Au-MnO2 could react with intratumoral H2O2 to produce O2 to enhance the type II photodynamic therapy(PDT),and Au NPs could decompose glucose to promote starving-like therapy.Besides,starving-like therapy can also produce H2O2 to increase O2 production.Simultaneously,MnO2 can consume glutathione(GSH)to enhance the antitumor efficacy,and the released Mn2+could be used for T1-weighted magnetic resonance imaging(MRI).Both in vitro and in vivo experiments had proven excellent cancer cell killing effect and antitumor efficacy of COF-Au-MnO2via such a cycle-like process.