Reversible pH-switchable NIR-II nano-photosensitizer for precise imaging and photodynamic therapy of tumors

Photodynamic therapy (PDT) has attracted widespread attention from researchers as an emerging cancer treatment method. There have been many reports on various types of NIR-II photosensitizers for imaging and treatment of tumor sites. However, there are few reports on the development of NIR-II organi...

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Published in:	Acta biomaterialia Vol. 188; pp. 315 - 328
Main Authors:	Chai, Yun, Sun, Ye, Sheng, Zhijia, Zhu, Yanyan, Du, Tianyou, Zhu, Bingjian, Yu, Hui, Dong, Bin, Liu, Yi, Wang, Hai-Yan
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 15-10-2024
Subjects:	Animals Cell Line, Tumor Female Humans Hydrogen-Ion Concentration Infrared Rays Mice Mice, Inbred BALB C Nanoparticles - chemistry Neoplasms - diagnostic imaging Neoplasms - drug therapy Neoplasms - pathology NIR-II pH-switchable Photochemotherapy - methods Photodynamic therapy Photosensitizers Photosensitizing Agents - chemistry Photosensitizing Agents - pharmacology Reactive Oxygen Species - metabolism ROS NIR-II Photodynamic therapy pH-switchable ROS Photosensitizers
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Summary:	Photodynamic therapy (PDT) has attracted widespread attention from researchers as an emerging cancer treatment method. There have been many reports on various types of NIR-II photosensitizers for imaging and treatment of tumor sites. However, there are few reports on the development of NIR-II organic small molecule photosensitizers that have intelligent response to the tumor microenvironment, precise imaging, real-time treatment, and high biocompatibility. In this work, we developed a series of NIR-II photosensitizers (RBTs) with near-infrared excitation, good photostability, and large Stokes shift. Among them, RBT-Br exhibited higher reactive oxygen species (ROS) generation efficiency due to the introduction of halogen heavy atoms to enhance intersystem crossing (ISC). It is noteworthy that RBT-Br can generate singlet oxygen (1O2) and superoxide anion radicals (•O2−) simultaneously under 730 nm laser. Subsequently, we used molecular engineering technology to construct three pH-responsive NIR-II photosensitizers (RBT-pHs) by utilizing the closure of the lactam ring, among which RBT-pH-1 (pKa = 6.78) is able to be directionally activated under the stimulation of tumor micro-acid environment, with its fluorescence emission window reaching 933 nm. Subsequently, RBT-pH-1 NPs encapsulated in DSPE-mPEG5k were applied for PDT treatment of mouse tumors. The results showed that RBT-pH-1 NPs were activated by the acidic tumor microenvironment and generated ROS under laser excitation, exhibiting precise tumor imaging and significant tumor growth inhibition. We look forward to these multifunctional NIR-II organic small molecule photosensitizers providing a more efficient approach for clinical treatment of tumors. A reversible pH-switchable NIR-II nano-photosensitizer RBT-pH-1 NPs (pKa = 6.76) is developed for precise imaging and PDT therapy of mouse tumors, which can be effectively used for targeted enrichment and activation of tumor micro-acid environments. The results show that this NIR-II photosensitizer generates ROS through tumor micro-acid environment stimulation and laser triggering, showing precise tumor imaging guidance and significant tumor growth inhibition. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1742-7061 1878-7568 1878-7568
DOI:	10.1016/j.actbio.2024.09.001