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载光敏剂的多功能壳聚糖纳米粒子用于原位成像、高效细菌生物膜清除和肿瘤消融。

Photosensitizer-Loaded Multifunctional Chitosan Nanoparticles for Simultaneous in Situ Imaging, Highly Efficient Bacterial Biofilm Eradication, and Tumor Ablation.

机构信息

School of Ophthalmology & Optometry, Eye Hospital , Wenzhou Medical University , Wenzhou 325027 , China.

Wenzhou Institute of Biomaterials and Engineering , Chinese Academy of Sciences , Wenzhou 325000 , China.

出版信息

ACS Appl Mater Interfaces. 2019 Jan 16;11(2):2302-2316. doi: 10.1021/acsami.8b19522. Epub 2018 Dec 31.

DOI:10.1021/acsami.8b19522
PMID:30596498
Abstract

In recent decades, bacterial and viral infections and chronic inflammatory response have emerged as important causes of cancer. Also, infections remain a significant cause of morbidity and mortality in cancer patients. In this work, carboxymethyl chitosan nanoparticles (CMC NPs) were synthesized in a facile and green way and further combined with ammonium methylbenzene blue (MB) as a cross-linking agent as well as a fluorescent molecule and a photosensitizer for self-imaging photodynamic therapy (PDT). The obtained CMC-MB NPs exhibited an apparent pH-responsive release behavior of MB, which was released for a prolonged period in a simulated physiological environment (pH 7.4) for more than 15 days and the time reduced to only 3.5 h in acidic conditions (pH 5.5). When irradiated by a 650 nm laser at 202 mW/cm for 5 min, the CMC-MB NPs showed efficient bactericidal and biofilm eradication properties as well as suppression of tumor cell growth in a similar acidified microenvironment. Furthermore, in an in vivo rabbit wound bacterial infection model, the rapid sterilization of CMC-MB NPs played a crucial role in bacterial infections, inflammation inhibition, and wound healing. As a PDT treatment against cancer, the CMC-MB NPs also exhibited an efficient antitumor therapeutic effect in a subcutaneous tumor mice model.

摘要

近几十年来,细菌和病毒感染以及慢性炎症反应已成为癌症的重要病因。此外,感染仍然是癌症患者发病率和死亡率的重要原因。在这项工作中,羧甲基壳聚糖纳米粒子(CMC NPs)通过简便且绿色的方法合成,并进一步与铵甲基苯蓝(MB)结合,作为交联剂以及荧光分子和光动力治疗(PDT)的光敏剂。所得的 CMC-MB NPs 表现出明显的 pH 响应性 MB 释放行为,在模拟生理环境(pH 7.4)中可长时间(超过 15 天)释放,而在酸性条件(pH 5.5)下则缩短至仅 3.5 h。当用 650nm 激光在 202 mW/cm 辐照 5 分钟时,CMC-MB NPs 在类似酸化的微环境中表现出高效的杀菌和生物膜清除特性以及抑制肿瘤细胞生长的特性。此外,在兔伤口细菌感染模型中,CMC-MB NPs 的快速杀菌作用在细菌感染、炎症抑制和伤口愈合中起着至关重要的作用。作为癌症的 PDT 治疗,CMC-MB NPs 在皮下肿瘤小鼠模型中也表现出高效的抗肿瘤治疗效果。

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