## 4 Applications of CDs in Cancer Theranosis
### Cancer Therapy via Drug Delivery, PTT, PDT, PTT+PDT, siRNA Delivery, SDT, and Gas Therapy
#### 4.2.3 PDT  
The PDT is a non-invasive cancer treatment method that utilizes photosensizers, light, and oxygen to generate ROS, which induces cancer cell apoptosis and necrosis. The PDT relies on the ability of photosensitizers to absorb light and transfer energy to nearby oxygen molecules, producing cytotoxic ROS such as singlet oxygen (\({}^{1}\)O\({}_{2}\)) and free radicals. In recent years, CDs have emerged as promising candidates for PDT due to their strong light absorption in the UV to NIR regions. CDs can serve as self-photosensitizers, which transfer energy to surrounding oxygen molecules [165; 166; 167]. Therefore, CDs alone can be used for PDT, but are less effective compared with conventional photosensitizers such as porphyrin. To enhance the effectiveness of PDT, CDs can be combined with traditional photosensizers such as porphyrin [168] and chlorin derivatives [39]. Although traditional photosensitizers are more powerful for PDT than CDs, their poor water solubility limits their PDT applications. For example, CDs conjugated with Ce6 highly enhanced the ROS production compared with Ce6 alone. In addition, CDs can be functionalized with targeting molecules such as FA to increase the selectivity for cancer cells, further improving the PDT efficiency [169; 170]. [PERSON] et al. prepared CDs using riboflavin as the carbon source and ethylenediamine as a cross-linking agent in a hydrothermal method and used 4T1-bearing mice to evaluate  
Figure 11: **(a)** (**i**) Photograph of CT26 cancer-bearing mouse: cancer is labeled with a red dotted circle after PTT and (**ii**) photographs of the excised cancers on the 11 th day after treatment. (**b**) Cancer volume growth of saline, CyCD, and CyCD + irradiation groups after treatment [162]. (**c**) Photographs of the cancer-bearing mice on different days after treatment and (**d**) relative cancer volume (V/V\({}_{0}\)) growth after treatment; C1 = CDs only, C2 = saline + laser, and PTT = CDs + laser (V: cancer volume and V\({}_{0}\): initial cancer volume before PTT) [163]. (**e**) Photographs of the cancer-bearing mice on the 15 th day after PTT, CD, laser, or saline treatments and (**f**) cancer volume change after treatment [164]. the effectiveness of PDT [171]. As shown in Figure 12a,b, the cancer volumes in the PDT-treated group (CDs + 365 nm UV light for 10 min) did not exhibit significant cancer growth over time, whereas the cancer volumes in the other treatment groups receiving either CDs only or light only, exhibited a rapid cancer growth similar to that of the control group. After two weeks of treatment, the PDT effectively inhibited the cancer growth, but did not reduce the cancer size due to the limited penetration depth of UV light. As a result, the authors suggested that this method will be more suitable for treating superficial skin cancers or inflammatory wounds. In a study by [PERSON] et al., porphyrin-based CDs (TPP CDs) were prepared using mono-hydroxylphenyl triphenylporphyrin (TPP) and chitosan in a hydrothermal method and used for PDT of hepatocarcinoma 22 (H22) xenograft models [168]. The TPP CDs exhibited excellent photostability, good water solubility, good biocompatibility, and efficient ROS generation upon 625 nm irradiation for 1 h. The results indicated a significant reduction in cancer size from 100 mm\({}^{3}\) to 56 mm\({}^{3}\) in the PDT group, while the saline control and TPP CD-only groups exhibited dramatic increases in cancer size to approximately 800 mm\({}^{3}\) (Figure 12c,d). Notably, TPP CDs were able to inhibit cancer growth more effectively (82.87%) than TPP (52.74%) owing to the poor water solubility of TPP. The incorporation of stable heteroatoms such as nitrogen or phosphorus into the CD structure has been shown to promote ROS generation [111]. For example, [PERSON] et al. synthesized nitrogen and phosphorus-co-doped red-emissive CDs (R-CDs) using o-phenylenediamine and phosphoric acid as the raw materials in a hydrothermal method, which enhanced the ROS production of \({}^{1}\)O\({}_{2}\)[165].