Adenosine triphosphate-responsive carbon dots nanoreactors for T_(1)-weighted magnetic resonance imaging-guided tumor chemodynamic therapy

三磷酸腺苷刺激响应型碳点纳米反应器用于T_1-增强的磁共振成像介导的化学动力学治疗

There are various strategies to conduct tumor microenvironment(TME)stimulus-responsive(e.g.,acid,H_(2)O_(2)or glutathione)nanoreactors for increasing the efficiency of chemodynamic therapy(CDT).Among these,the exploitation of adenosine triphosphate(ATP,another overexpressed biomarker in TME)-responsive nanoreactors for tumor CDT is still challenging.Herein,the ATP-responsive iron-doped CDs(FeCDs)were firstly prepared and then coassembled with glucose oxidase(GOx)to obtain FeCDs/GOx liposomes as ATP-responsive nanoreactors.Under TME conditions,the nanoreactors initially released FeCDs and GOx.Subsequently,with the existence of ATP,iron ions were rapidly released from the FeCDs to trigger Fenton/Fenton-like reactions for generating·OH.Meanwhile,the T_(1)-weighted magnetic resonance imaging(MRI)was achieved due to the released iron ions.Moreover,the GOx converted endogenous glucose in tumor to gluconic acid and H_(2)O_(2)to satisfy the requirement of·OH generation.In vitro as well as in vivo experiments illustrated that the obtained ATP-responsive CD nanoreactors could be used as a versatile nanotheranostics for simultaneously T_(1)-weighted MRI-guided tumor CDT.This work presents a new ATP-responsive nanoreactor with selfsupplied H_(2)O_(2)for multifunctional nanotheranostic applications.

设计合成具有肿瘤微环境(如酸、H_(2)O_(2)、谷胱甘肽等)刺激响应型纳米反应器来提高化学动力学治疗(CDT)效果引起了研究者们的广泛关注.目前,探索具有三磷酸腺苷(ATP)刺激响应型纳米反应器用于肿瘤CDT具有重要意义.在此,我们首先制备了具有ATP刺激响应型的铁掺杂碳点(FeCDs).随后利用脂质体将FeCDs与葡萄糖氧化酶(GOx)共组装,得到ATP刺激响应型的纳米反应器.在肿瘤组织中,该纳米反应器首先释放FeCDs与GOx.在ATP刺激下,铁离子能够快速从FeCDs上释放下来引发Fenton/Fenton-like反应产生·OH,实现CDT.于此同时释放的铁离子能够提高材料T_1增强的磁共振成像.并且GOx能够在肿瘤中将葡萄糖转化为H_(2)O_(2),进而增加·OH的产量,提高CDT治疗效果.本研究提供了一种新型ATP刺激响应型且具有自补充H_(2)O_(2)功能的纳米反应器用于肿瘤诊断与治疗.