## 4 Applications of CDs in Cancer Theranosis
### Cancer Therapy via Drug Delivery, PTT, PDT, PTT+PDT, siRNA Delivery, SDT, and Gas Therapy
#### 4.2.5 siRNA Therapy  
The siRNA therapy is a promising alternative for the treatment of cancer [180; 181; 182]. It lies in the use of effective carriers of siRNA into cancer cells. One valuable strategy emerging in this field is the use of CDs as siRNA carriers, which are small in size with unique optical properties, good water solubility, and good biocompatibility. The charge interactions between CDs and siRNA are the key to successful siRNA transfer. The siRNA possesses a negative charge due to the presence of phosphate groups in its backbone structure, making it necessary for CDs to possess a positive charge through surface modifications with positively charged molecules such as PEI. In addition, the fluorescence properties of CDs facilitate tracking of their delivery. Several studies have demonstrated the potential use of CDs in siRNA delivery and therapy [183; 184; 185; 186; 187; 188; 189; 46; 153; 183; 184; 185; 186; 187; 188; 46; 189]. [PERSON] et al. performed targeted siRNA delivery using LAAM GUA-CDs for cancer therapy of HeLa cancer-bearing mice in which the LAAM GUA-CDs enabled efficient siRNA loading and targeted delivery to the cancer site [153]. The Bcl-2 siRNA (siBcl-2) can downregulate the antiapoptotic protein Bcl-2 expression in cancer cells, which is responsible for inhibiting cancer cell growth. They demonstrated that LAAM GUA-CDs/siBcl-2 achieved a 78% gene silencing efficiency in vitro and a cancer inhibition efficiency of 68% in vivo, as shown in Figures 14a and 14b, respectively. Notably, the transfection efficiency of LAAM GUA-CDs/siBcl-2 was twice as high as that of transfection reagent Lipofectamine2000 conjugates with siBcl-2 (Lipo2000/siBcl-2), making LAAM GUA-CDs/siBcl-2 a promising tool for gene cancer therapy. [PERSON] et al. performed a study to evaluate the efficacy of the DOX and siRNA co-delivery system (i.e., CD-PEI-DOX-siMRP1) in inhibiting cancer growth using lung cancer xenograft models in nude mice [188]. The siRNA targeted the multidrug-resistant proteins MRP1 in lung cancer to down-regulate them and consequently, enhance the chemotherapy efficiency of DOX. The CD-PEI-DOX-siMRP1 exhibited a considerably stronger signal in the cancer site than the DOX group, owing to its enhanced cancer targeting. As shown in Figure 14c,d, the cancers treated with CD-PEI-DOX-siMRP1 were considerably smaller than those of the other treatment groups, demonstrating that the co-delivery system was superior to the other treatments in effectively inhibiting cancer growth. [PERSON] et al. developed an efficient siRNA delivery system using CD-PEI to effectively knock down the vascular endothelial growth factor (VEGF) gene expression in vitro and in vivo [185]. They investigated the anticancer efficacy of the siRNA/CD-PEI in a human breast cancer xenograft mouse model through IV administration of siVEGF/CD-PEI. The results indicated a significant inhibition of cancer growth in the siVEGF/CD-PEI-treated group, as illustrated in Figure 14e, whereas the groups treated with CD-PEI and free siVEGF did not exhibit any significant changes in cancer size compared to the control group. The authors demonstrated that the CD-PEI not only facilitated effective siRNA delivery but also protected the siRNA from degradation, thereby enhancing its therapeutic efficacy in vivo. [PERSON] et al. developed fluorescent CD (FCD)-based Plk1 targeting siRNA (siPlk1) (C-siPlk1) to perform in vivo cancer inhibition experiments using Balb/c nude mice implanted with human melanoma cancer (A375) cells [183]. The C-siPlk1 down-regulated the expression of polo-like kinase-1 (Plk1), a master regulator of mitosis. After one week of the treatment, C-siPlk1 demonstrated significant efficacy in inhibiting cancer growth compared to the other groups (Figure 14f), in which the cancer volumes in the PBS-only, FCDs-only, and FCDs/scrambled siRNA (C-Scram) groups increased sharply. In addition, the administration of free siPlk1 and Lipo2000/siPlk1 resulted in at least a four-fold increase in cancer volume compared to the pre-treatment levels.