An Activatable Phototheranostic Nanoplatform for TumorSpecific NIR-II Fluorescence Imaging and Synergistic NIR-IIPhotothermal-Chemodynamic Therapy

NIR-II荧光成像和协同NIR-II光热化学动力学治疗的肿瘤特异性可激活光治疗纳米平台

主讲人：梁惠闲

Small ( IF 13.3 ) PubDate : 2023-02-28 , DOI: 10.1002/smll.202206053Abstract

Abstract:

           The phototheranostics in the second near-infrared window (NIR-II) have proven to be promising for the precise cancer theranostics. However, the non-responsive and “always on” imaging mode lacks the selectivity, leading to the poor diagnosis specificity. Herein, a tumor microenvironment (TME) activated NIR-II phototheranostic nanoplatform (Ag2S-Fe(III)-DBZ Pdots, AFD NPs) is designed based on the principle of Förster resonance energy transfer (FRET). The AFD NPs are fabricated through self-assembly of Ag2S QDs (NIR-II fluorescence probe) and ultra-small semiconductor polymer dots (DBZ Pdots, NIR-II fluorescence quencher) utilizing Fe(III) as coordination nodes. In normal tissues, the AFD NPs maintain in “off” state, due to the FRET between Ag2S QDs and DBZ Pdots. However, the NIR-II fluorescence signal of AFD NPs can be rapidly “turn on” by the overexpressed GSH in tumor tissues, achieving a superior tumor-to-normal tissue (T/NT) signal ratio. Moreover, the released Pdots and reduced Fe(II) ions provide NIR-II photothermal therapy (PTT) and chemodynamic therapy (CDT), respectively. The GSH depletion and NIR-II PTT effect further aggravate CDT mediated oxidative damage toward tumors, achieving the synergistic anti-tumor therapeutic effect. The work provides a promising strategy for the development of TME-activated NIR-II phototheranostic nanoprobes.

摘要：

         第二个近红外窗口（NIR-II）中的光热分析已被证明有希望用于精确的癌症热分析。然而，非响应性和“常开”成像模式缺乏选择性，导致诊断特异性差。在此，基于FRET原理，设计了肿瘤微环境（TME）激活的NIR-II光透明纳米平台（Ag2S-Fe（III）-DBZ-Pdots，AFD NPs）。AFD NP是通过利用Fe（III）作为配位节点的Ag2S量子点（NIR-II荧光探针）和超小型半导体聚合物点（DBZ-Pdots，NIR-II萤光猝灭剂）的自组装制备的。在正常组织中，由于AgS量子点和DBZ-Pdots之间的FRET，AFD NP保持在“关闭”状态。然而，AFD NPs的NIR-II荧光信号可以被肿瘤组织中过表达的GSH快速“开启”，从而实现优越的肿瘤与正常组织（T/NT）信号比。此外，释放的Pdots和还原的Fe（II）离子分别提供NIR-II光热治疗（PTT）和化学动力学治疗（CDT）。GSH耗竭和NIR-II PTT效应进一步加重CDT介导的对肿瘤的氧化损伤，达到协同抗肿瘤治疗效果。这项工作为TME激活的NIR-II光电性纳米探针的开发提供了一种有前景的策略。