Development of Sulfonamide-Functionalized Charge-Reversal AIE Photosensitizers for Precise Photodynamic Therapy in the Acidic Tumor Microenvironment |
| |
| Authors: | Xueqin Yang Changhuo Xu Xun Zhang Pei Li Feiyi Sun Xinyue Liu Xinyuan Wang Ryan T. K. Kwok Jinglei Yang Jacky W. Y. Lam Yongye Liang Ben Zhong Tang |
| |
| Affiliation: | 1. Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Mechanical and Aerospace Engineering, and Guangdong-Hong Kong-Macau Joint Laboratory of Optoelectronic and Magnetic Functional Materials, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077 China;2. Department of Materials Science and Engineering, Southern University of Science and Technology, Guangdong, 518055 China;3. Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Mechanical and Aerospace Engineering, and Guangdong-Hong Kong-Macau Joint Laboratory of Optoelectronic and Magnetic Functional Materials, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077 China Department of Materials Science and Engineering, Southern University of Science and Technology, Guangdong, 518055 China |
| |
| Abstract: | Tumor-targeted photodynamic therapy (PDT) is desirable as it can achieve efficient killing of tumor cells with no or less harm to normal cells. Herein, a facile molecular engineering strategy is developed for photosensitizers (PSs) with aggregation induced emission (AIE) characteristics and responsive properties to the acidic tumor microenvironment (TME). By the marriage of pH-sensitive sulfonamide moieties with AIE PSs, two near-infrared AIE luminogens called DBP-SPy and DBP-SPh are designed and synthesized. Both luminogens can form negatively charged nanoaggregates in the aqueous medium at physiological pH. The DBP-SPy nanoaggregates undergo surface charge conversion to become positive at pH close to the signature pH of TME, while DBP-SPh nanoaggregates show no such property. The endowed response to acidic TME enables the enhanced cellular uptake of DBP-SPy at pH = 6.8. By contrast, its cellular uptake is much sacrificed at pH 7.4. As a result, under white light irradiation, DBP-SPy nanoaggregates demonstrate a considerable photodynamic therapeutic effect on cancer cells in vitro and excellent tumor growth inhibition in vivo. Hence, this study not only provides an acidic TME-responsive AIE PS for precise PDT, but also inspires new design strategies for AIE-based theragnostic systems with targeting characteristics. |
| |
| Keywords: | acidic tumor microenvironment aggregation-induced emission photosensitizers pH-responsibility targeted photodynamic therapy |
|
|
