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锰(II)导向的双光敏剂共聚组装体用于多模态成像引导的自增强光疗。

Mn(II)-directed dual-photosensitizers co-assemblies for multimodal imaging-guided self-enhanced phototherapy.

机构信息

Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, China.

Department of Biomaterials, College of Materials, Research Center of Biomedical Engineering of Xiamen & Key Laboratory of Biomedical Engineering of Fujian Province & Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen 361005, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Oct;129:112351. doi: 10.1016/j.msec.2021.112351. Epub 2021 Jul 31.

Abstract

Phototherapy has attracted increasing attention in cancer therapy owing to its non-invasive nature, high spatiotemporal selectivity, and negligible side effects. However, a single photosensitizer often exhibits poor photothermal conversion efficiency or insufficient reactive oxygen species (ROS) productivity. Even worse, the ROS can be consumed by tumor overexpressed reductive glutathione, resulting in severely compromised phototherapy. In this paper, we prepared a Mn-coordination driven dual-photosensitizers co-assemblies (IMCP) for imaging-guided self-enhanced PDT/PTT. Specifically, a photothermal agent indocyanine green (ICG), a photodynamic agent chlorin e6 (Ce6), and a transition metal ion (Mn) were chosen to synthesize the nanodrug via coordination-driven co-assembly. The as-prepared IMCP exhibited extremely high photosensitizer payload (96 wt%), excellent physiological stability, and outstanding tumor accumulation. Moreover, the existence of Mn not only assists the nanostructure formation but also could competitively coordinate with GSH to minimize the unnecessary ROS consumption, thus improving PDT efficiency. Meanwhile, benefiting from the intrinsic fluorescence, photoacoustic imaging ability of photosensitizers, and the MRI contrast potential of Mn, IMCP exhibited superior imaging potential for guiding tumor phototherapy. By changing the excitation wavelength suitably, IMCP could realize the switch between PTT and PDT. In short, the dual-PSs co-assembled nanotheranostic has great potential for multi-modal imaging guided phototherapy.

摘要

光疗因其非侵入性、高时空选择性和可忽略的副作用而在癌症治疗中受到越来越多的关注。然而,单一的光敏剂往往表现出较差的光热转换效率或不足的活性氧(ROS)产生能力。更糟糕的是,ROS 可以被肿瘤过度表达的还原型谷胱甘肽消耗,从而严重影响光疗效果。在本文中,我们制备了一种锰配位驱动的双光敏剂共组装体(IMCP),用于成像引导的自增强 PDT/PTT。具体来说,选择光热剂吲哚菁绿(ICG)、光敏剂氯乙酮(Ce6)和过渡金属离子(Mn)通过配位驱动共组装合成纳米药物。所制备的 IMCP 表现出极高的光敏剂负载量(96wt%)、优异的生理稳定性和出色的肿瘤积累能力。此外,Mn 的存在不仅有助于纳米结构的形成,还可以与 GSH 竞争配位,最大限度地减少不必要的 ROS 消耗,从而提高 PDT 效率。同时,得益于光敏剂的固有荧光、光声成像能力和 Mn 的 MRI 对比潜力,IMCP 表现出优异的用于指导肿瘤光疗的成像潜力。通过适当改变激发波长,IMCP 可以实现 PTT 和 PDT 之间的切换。总之,双 PSs 共组装纳米诊疗剂具有用于多模态成像引导光疗的巨大潜力。

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