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<p>Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment due to high spatiotemporal selectivity. However, most of the conventional photosensitizers (as the core component of PDT) are activated by visible light, which suffers from limited tissue penetration, thereby restricting the clinical applications of PDT. In this study, two carboxymethyl-functionalized aggregation-induced emission (AIE) compounds, (E)-2-(4-(bis(4-methoxyphenyl)amino)styryl)-5-carboxy-3-methylbenzo[d]thiazol-3-ium (MOTBAC) and (E)-5-carboxy-2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-3-methylbenzo[d]thiazol-3-ium (TTBAC), were synthesized and coordinated with upconversion nanoparticles (UCNPs) to form UCNPs-MOTBAC and UCNPs-TTBAC nanoconjugates, which generate reactive oxygen species (ROS) under 980-nm irradiation. The energy transfer efficiencies from UCNPs to MOTBAC and TTBAC were 29.4% and 33.9%, respectively. To enhance TTBAC loading, TTBAC was silanized and covalently grafted onto the UCNPs@mSiO<sub>2</sub>, while free TTBAC molecules were incorporated into the porous silica network. The resulting nanoparticles were further modified with DSPE-PEG<sub>2000</sub> to obtain USiTT. Compared with UCNPs-TTBAC nanoconjugates, the USiTT nanoparticles exhibited increased TTBAC loading (5.08% vs. 4.20%), higher encapsulation efficiency (95.88% vs. 79.30%), and enhanced energy transfer efficiency (38.78%). Cellular uptake experiments revealed that USiTT primarily accumulated at lysosomes. Phototoxicity assays and live/dead cell staining experiments demonstrated that the UCNPs in USiTT could activate TTBAC and generate ROS, resulting in cancer cell ablation. The method of constructing USiTT nanoparticles could effectively enhance the loading capacity of photosensitizers and improve energy transfer of UCNPs, ensuring that ROS could be effectively generated under NIR irradiation. Furthermore, the nanomaterials can target the lysosome, which offered a potential strategy for the development of NIR-activated nanomaterials in precision photodynamic therapy.</p>

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Developing FRET-based UCNP@SiO2-AIE/AIE@DSPE-PEG2000 nanomaterials for lysosome-targeted NIR photodynamic cancer therapy

  • 期刊论文

  • 发表日期：

    2025年11月15日

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  • Yuanhang Li,
  • Xing Wang,
  • Li Yang,
  • Xudong Xie,
  • Shengnan Yao,
  • Tian Min,
  • Zhengjian Qi

摘要

Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment due to high spatiotemporal selectivity. However, most of the conventional photosensitizers (as the core component of PDT) are activated by visible light, which suffers from limited tissue penetration, thereby restricting the clinical applications of PDT. In this study, two carboxymethyl-functionalized aggregation-induced emission (AIE) compounds, (E)-2-(4-(bis(4-methoxyphenyl)amino)styryl)-5-carboxy-3-methylbenzo[d]thiazol-3-ium (MOTBAC) and (E)-5-carboxy-2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-3-methylbenzo[d]thiazol-3-ium (TTBAC), were synthesized and coordinated with upconversion nanoparticles (UCNPs) to form UCNPs-MOTBAC and UCNPs-TTBAC nanoconjugates, which generate reactive oxygen species (ROS) under 980-nm irradiation. The energy transfer efficiencies from UCNPs to MOTBAC and TTBAC were 29.4% and 33.9%, respectively. To enhance TTBAC loading, TTBAC was silanized and covalently grafted onto the UCNPs@mSiO2, while free TTBAC molecules were incorporated into the porous silica network. The resulting nanoparticles were further modified with DSPE-PEG2000 to obtain USiTT. Compared with UCNPs-TTBAC nanoconjugates, the USiTT nanoparticles exhibited increased TTBAC loading (5.08% vs. 4.20%), higher encapsulation efficiency (95.88% vs. 79.30%), and enhanced energy transfer efficiency (38.78%). Cellular uptake experiments revealed that USiTT primarily accumulated at lysosomes. Phototoxicity assays and live/dead cell staining experiments demonstrated that the UCNPs in USiTT could activate TTBAC and generate ROS, resulting in cancer cell ablation. The method of constructing USiTT nanoparticles could effectively enhance the loading capacity of photosensitizers and improve energy transfer of UCNPs, ensuring that ROS could be effectively generated under NIR irradiation. Furthermore, the nanomaterials can target the lysosome, which offered a potential strategy for the development of NIR-activated nanomaterials in precision photodynamic therapy.