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锡(IV)-卟啉类用于光动力抗癌和抗菌化疗。

Sn(IV)-porphyrinoids for photodynamic anticancer and antimicrobial chemotherapy.

机构信息

Institute for Nanotechnology Innovation, Rhodes University, Makhanda, 6140, South Africa.

Department of Chemistry, SRM University - AP, Amaravati, Andhra Pradesh, 522502, India.

出版信息

Dalton Trans. 2023 Apr 25;52(16):5000-5018. doi: 10.1039/d3dt00603d.

Abstract

Photodynamic therapy (PDT) is a mode of treatment for different types of cancers, which involves a nontoxic photosensitizer (PS), a light source to activate the PS, and ground-state molecular oxygen (O). Light activation of the PS leads to the generation of reactive oxygen species (ROS), which initiates a toxic effect on the surrounding cellular substrates, thereby destroying the cancerous cells. The commercially used PDT drug Photofrin which is a tetrapyrrolic porphyrin-based photosensitizer has drawbacks such as aggregation in water, prolonged skin photosensitivity, variability in chemical compositions, and minimal absorbance in the red-light region. Metallation of the porphyrin core with diamagnetic metal ions aids the photogeneration of singlet oxygen (ROS). Metalating with Sn(IV) provides a six-coordination octahedral geometry with -diaxial ligands. This approach suppresses aggregation in aqueous media and increases ROS generation upon light exposure due to the heavy atom effect. Bulky -diaxial ligation hinders the approach of the Sn(IV) porphyrins, thereby suppressing aggregation effects. In this review, we document the recently reported Sn(IV) porphyrinoids and their photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity properties. In a similar manner to PDT, the photosensitizer is used to kill the bacteria upon irradiation with light during PACT. Often, bacteria develop resistance against conventional chemotherapeutic drugs over time, decreasing their antibacterial properties. However, in the case of PACT, it is difficult to generate resistance against singlet oxygen produced by the photosensitizer.

摘要

光动力疗法(PDT)是治疗不同类型癌症的一种方法,它涉及一种无毒的光敏剂(PS)、一种激活 PS 的光源和基态分子氧(O)。PS 的光激活导致活性氧物质(ROS)的产生,这会对周围的细胞基质产生毒性作用,从而破坏癌细胞。目前市售的 PDT 药物 Photofrin 是一种基于四吡咯啉的卟啉类光敏剂,存在着在水中聚集、皮肤光敏感性延长、化学成分变化、在红光区吸收最小等缺点。卟啉核心与抗磁性金属离子的金属化有助于单线态氧(ROS)的光生成。Sn(IV)的金属化提供了一个六配位的八面体几何形状和 -diaxial 配体。这种方法抑制了在水介质中的聚集,并由于重原子效应增加了光照下 ROS 的产生。体积庞大的 -diaxial 键合阻碍了 Sn(IV)卟啉的接近,从而抑制了聚集效应。在这篇综述中,我们记录了最近报道的 Sn(IV)卟啉及其光动力疗法(PDT)和光动力抗菌化疗(PACT)活性特性。与 PDT 类似,在 PACT 中,当用光照照射时,光敏剂被用来杀死细菌。通常,随着时间的推移,细菌会对常规化疗药物产生耐药性,降低其抗菌特性。然而,在 PACT 的情况下,很难对光敏剂产生的单线态氧产生耐药性。

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