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  • br Hemolysis assay br The blood compatibility is


    3.5. Hemolysis assay
    The blood compatibility is a critical parameter for in vivo application of nanotherapeutics [38]. As presented in Fig. S3a,b, there was no distinguishable evidence of hemolysis for erythrocytes treated with CS-CPT-NPs under the CPT concentration of 100 μM, which was sig-nificantly higher than the concentrations applied in cell experiments. Additionally, in vivo hemocompatibility results (Fig. S3c) indicated that all the tested blood parameters, including red blood Elafibranor (RBC), he-moglobin (HGB), mean cell hemoglobin (MCH) and mean corpuscular 
    hemoglobin concentrations (MCHC), were in the normal range. Taken together, these results imply that CS-CPT-NPs have excellent blood biocompatibility, and can be safely used for intravenous administration.
    3.6. In vivo anti-colon cancer activities of NPs
    To verify the anti-cancer efficacy of NPs in vivo, PBS, CUL-CPT-NPs and CS-CPT-NPs were intravenously injected into mice bearing a sub-cutaneous colon tumor. The change of body weight is a common parameter for assessing the systemic adverse effects of nanother-apeutics [39]. It could be noticed from Fig. 5a that intravenous ad-ministration of NPs resulted in no notably body weight loss compared with the PBS control group, indicating the comparable safety of CUL-CPT-NPs and CS-CPT-NPs. The tumor volumes for the different treat-ment groups are displayed in Fig. 5b,c. The volume of colon tumor treated with PBS increased throughout the entire experiment. However, the trend of increasing tumor volume was retarded by NP treatments. Furthermore, intravenous injection of CUL-CPT-NPs and CS-CPT-NPs decreased tumor volumes by 37.5% and 43.7%, respectively. The im-proved suppression of tumor volume in CS-CPT-NP-treated group could be attributed to the colon tumor-targeting property of CS-functionalized NPs. In addition, we found that the tumor weights (Fig. 5d) correlated well with their sizes.
    Histological analysis of tumor tissue sections (Fig. 6a) were carried out to compare the morphology of tumor tissue between PBS control group and NP-treated groups. Tumor cells in the PBS control group were observed with large nucleus. On the contrary, NP-treated groups showed decreased tumor cell numbers and nucleus shrinkage. It was
    Fig. 6. (a) H&E staining of tumor tissues from mice treated with CUL-CPT-NPs or CS-CPT-NPs. Scale bar represents 50 μm. (b) Representative images of double-fluorescence labeling with DAPI (nuclei, blue) and TUNEL (green) in colon tumors from different mouse groups. Scale bar represents 20 μm (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
    interesting to note that a large necrotic area was detected in the tumor tissues from CS-CPT-NP-treated group. The pro-apoptotic effects of CS-CPT-NPs were further studied using TUNEL assays. Fig. 6b showed that TUNEL-positive cells (green fluorescence) was barely observed in the tumor tissue sections from PBS control group, but was obviously de-tected in tumor tissue sections of mice treated with CUL-CPT-NPs. Furthermore, CS-CPT-NP-treated group showed much more green fluorescence than CUL-CPT-NPs, indicating that CS-CPT-NPs had much stronger pro-apoptotic activity than CUL-CPT-NPs in vivo. In addition, to corroborate the safety of the treatments, we performed histological analysis of the major organs (heart, liver, spleen, lung and kidney). It was found that no clear evidence of organ or tissue impairments was observed in the H&E-stained sections from all the treatment groups (Fig. S4), demonstrating that CUL-CPT-NPs and CS-CPT-NPs were well tolerated by organisms. 
    4. Conclusions
    In this study, chondroitin sulfate (CS)-functionalized camptothecin (CPT)-loaded polymeric nanoparticles (NPs) were constructed. The obtained CS-CPT-NPs had an average hydrodynamic particle size (about 289 nm), excellent monodispersity and electro-neutral surface (around + 0.12 mV), as well as good stability in biological environ-ment. We found that CS-CPT-NPs had excellent in vitro colon cancer-targeting capacity, and showed improved anti-colon cancer activities compared to non-targeted NPs. Importantly, animal experiments clearly suggested that CS-CPT-NPs exhibited favorable blood compatibility, and much higher anti-colon cancer activities than CUL-CPT-NPs. Collectively, our findings indicate the promising potential of CS-CPT-NPs as a nanotherapeutic platform for colon cancer-targeted che-motherapy.
    Conflict of interest
    The authors declare no competing financial interest.
    This work was supported by the National Natural Science Foundation of China (51503172 and 81571807), the Young Core Teacher Program of the Municipal Higher Educational Institution of Chongqing, the Venture & Innovation Support Program for Chongqing Overseas Returnees (cx2018029), the Graduate Student Research Innovation (CYS18108), the Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices and the State Key Laboratory of Silkworm Genome Biology.