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用于缺氧肿瘤的非氧依赖性协同光热/光动力治疗的单线态氧共价有机框架纳米载体。

Covalent Organic Framework Nanocarriers of Singlet Oxygen for Oxygen-Independent Concurrent Photothermal/Photodynamic Therapy to Ablate Hypoxic Tumors.

机构信息

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.

School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.

出版信息

Small. 2022 Sep;18(37):e2202369. doi: 10.1002/smll.202202369. Epub 2022 Aug 15.

DOI:10.1002/smll.202202369
PMID:35971160
Abstract

Photodynamic therapy (PDT) of cancers is seriously restricted by tumor hypoxia. In addition to the intrinsic hypoxic microenvironment, continuous photoirradiation further aggravates intratumoral hypoxia, thereby reducing the PDT effect significantly. Oxygen-independent PDT is recognized as an efficient approach to overcome this issue. Herein, singlet oxygen ( O )-stored covalent organic framework (COF) nanoparticles loading the near-infrared (NIR) dye cypate, which realize oxygen-independent O production for concurrent photothermal therapy (PTT) and PDT under NIR irradiation, are presented. The cypate-loading COF nanoparticles are prepared by using the photosensitizers and O -stored molecules via formation of Schiff base bonds, followed by coverage of poly(vinyl pyrrolidone). The COF nanoparticles significantly improve the photostability and photothermal conversion efficiency of cypate by protecting them from photodegradation under NIR irradiation. Upon 660 nm laser irradiation, O is produced by the photosensitizer motifs and is successfully stored by the O -stored moieties. After intravenous injection and tumor accumulation, the COF nanoparticles can generate heat quickly upon 808 nm irradiation which induces the efficient release of the stored O to ablate tumors via O -independent concurrent PTT/PDT. Accordingly, the COF nanocarriers of O provide a paradigm to develop O -independent concurrent PTT/PDT for precise cancer treatment upon NIR irradiation.

摘要

光动力疗法(PDT)治疗癌症受到肿瘤乏氧的严重限制。除了内在的乏氧微环境外,连续的光照射进一步加重了肿瘤内缺氧,从而显著降低了 PDT 效果。氧非依赖性 PDT 被认为是克服这一问题的有效方法。本文报道了一种负载近红外染料 cypate 的单线态氧( 1 O )存储共价有机框架(COF)纳米粒子,可在近红外光照射下实现氧非依赖性 1 O 产生,用于协同光热治疗(PTT)和 PDT。通过席夫碱键的形成,将光敏剂和 1 O 存储分子用于制备载 cypate 的 COF 纳米粒子,然后用聚(N-乙烯基吡咯烷酮)覆盖。COF 纳米粒子通过在近红外光照射下保护 cypate 免于光降解,显著提高了 cypate 的光稳定性和光热转换效率。在 660nm 激光照射下,通过光敏剂基元产生 1 O ,并通过 1 O 存储基元成功存储。静脉注射和肿瘤积累后,COF 纳米粒子在 808nm 照射下能迅速产生热量,通过 1 O 非依赖性协同 PTT/PDT 有效地释放存储的 1 O 来消融肿瘤。因此, 1 O 存储的 COF 纳米载体为在近红外光照射下开发氧非依赖性协同 PTT/PDT 以进行精确的癌症治疗提供了范例。

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