Additional file 1 of In vivo toxicity evaluation of tumor targeted glycol chitosan nanoparticles in healthy mice: repeated high-dose of glycol chitosan nanoparticles potentially induce cardiotoxicity

Additional file 1: Figure S1. Synthetic route to prepare the glycol chitosan and 5β-cholanic acid conjugates. Figure S2. Detail information of average size of different concentrations of CNPs in the mouse serum. Figure S3. Detail information of average size of different concentrations of CNPs in the mouse serum (n=5). Figure S4. Flow cytometric results showing H9C2 cells stained with Annexin V/PI after treatment with CNPs for 24 h. Figure S5. Fluorescence image of major organs from mice treated with 90 mg/kg of CNPs for 7 days. Fluorescence intensities were normalized with the results of Figure 3B and 3C. Figure S6. Excretion profile of Cy5.5-CNPs after 90 mg/kg treatment. The urines were collected from the mice at the indicated time points, followed by analysis of Cy5.5 fluorescence intensity using HPLC. Figure S7. Detail information of hematological parameters on day 7 after single- or multi-dose of 10, 22.5 or 90 mg/kg CNPs. Figure S8. Detail information of complete cell count results on day 7 after single- or multi-dose of 10, 22.5 or 90 mg/kg CNPs (n=5). Figure S9. Uncropped images of western blot results in Figure 5E

Additional file 1 of Preclinical development of carrier-free prodrug nanoparticles for enhanced antitumor therapeutic potential with less toxicity

Additional file 1: Figure S1. Synthetic route to prepare the cancer-specific prodrug FRRG-DOX. Figure S2. The (a) purity, (b) exact mass and (c) chemical structure of FRRG-DOX, as confirmed via HPLC, MALDI-TOF and 1H-NMR, respectively. Figure S3. Detail information of the particle stability analysis of (a) FRRG-DOX and (b) F68-FDOX nanoparticles in mouse serum. Figure S4. Cumulative release of G-DOX from F68-FDOX after incubation with cathepsin B. Figure S5. Cleavage behavior of FRRG-DOX after incubation with cathepsin B. Figure S6. The mass analysis of the newly appeared peak (13 min; Fig. 1f) in the HPLC spectrum after incubation of F68-FDOX with cathepsin B. Figure S7. Long-term storage stability of lyophilized F68-FDOX powder stored for (a) 3, (b) 6, (c) 12 months in the low (-4 °C) condition. Figure S8. Long-term storage stability of lyophilized F68-FDOX powder stored for (a) 3, (b) 6, (c) 12 months in the room (37 °C) condition. Figure S9. Long-term storage stability of lyophilized F68-FDOX powder stored for (a) 3, (b) 6, (c) 12 months in the accelerated (60 °C) condition. Figure S10. The cellular uptake of F68-FDOX and DOX in the HT29, MDA-MB231, KPC960 and H9C2 cells after 6 or 24 h of incubation. Figure S11. The fluorescence intensity profile was measured from the line-scans through cells of white lines in the fluorescence imaging results in Fig. 2b. Figure S12. The mass analysis of the DOX released from F68-FDOX in the HT29, MDA-MB231 and KPC960 cells after 48 h of treatment. Figure S13. The cell viability of HT29, MDA-MB231, KPC960 and H9C2 cells after 48 h treatment with FRRG-DOX. Figure S14. Quantitative analysis for the fluorescence intensity in major organs and tumor tissues of HT29-tumor bearing mice after 9 h of treatment with DOX, FRRG-DOX or F68-FDOX. Figure S15. Quantitative analysis for the apoptosis region of tumor tissues stained with TUNEL. Figure S16. Mice survival after single-dosage with DOX, FRRG-DOX or F68-FDOX. Figure S17. Detail information of the serological examination on day 9 after single-dosage with DOX, FRRG-DOX or F68-FDOX. Figure S18. Detail information of the complete blood count (CBC) analyses on day 9 after single-dosage with DOX, FRRG-DOX or F68-FDOX. Figure S19. Major organ tissues stained with TUNEL on day 9 after single-dosage with DOX, FRRG-DOX or F68-FDOX. Figure S20. Mice survival after multi-dosage with DOX, FRRG-DOX or F68-FDOX. Figure S21. Detail information of the hematological analyses on day 9 after multi-dosage with DOX, FRRG-DOX or F68-FDOX

Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor

Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN–CNPs) and integrin αvβ3 with cyclic RGD-conjugated CNPs (cRGD–CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN–CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD–CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN–CNPs could bind artificial azide reporters on tumor cells more uniformly (∼92.9%) compared to cRGD–CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy

Additional file 1 of Liposomes targeting the cancer cell-exposed receptor, claudin-4, for pancreatic cancer chemotherapy

Additional file 1: Figure S1. Storage stability,measured as changes in the size and PDI of D@C-LPs at 4°C and 25°C. Figure S2. Cytotoxicity of Dox-loaded liposomes against various cancer cell lines. Figure S3. In vivo biodistribution of D@C-LP with pre-treatment of CLDN4 antibody. Figure S4. In vivo therapeutic efficacy of Dox-loaded liposomes in a KPC960 xenograft model. A Photographs of excised tumors after treatment. B Ex vivo fluorescence images. C Changes in body weight in treatment groups over the course of 15 days. D H&E staining of major organsafter 15 days. Figure S5. In vivo therapeutic efficacy of Dox-loaded liposomes in a KPC960 orthotopic model. A Average tumor weights of excised primary tumors. B Average tumor weights of excised metastatic tumors. C Changes in body weight in treatment groups over the course of 24 days. D H&E staining of major organsafter 24 days

Additional file 1 of Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light

Supplementary Material

Additional file 2 of Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light

Supplementary Material