br Female nude mice weeks
Female nude mice (5–7 weeks old) were obtained from Jiangsu KeyGEN BioTECH Corp., Ltd. All performance of in vivo experiments was in line with the institutional animal use and care regulations ap-proved by of Nanjing Normal University. The flank of each nude mouse was subcutaneously injected with MCF-7/ADR cells.
The intravenous injection of BPNs-PDA-PEG-PEITC-Mn/DOX (100 μL, 10 mg/kg) in tumor-bearing mice which were used to perform the in vivo MRI. The MRI photos were obtained through Bruker Icon 1.0 T scanning mice at different time points.
3.21. In vivo synergistic treatment
When the tumor volumes of nude mice had become to 100 mm3, separating the mice into ten groups (n = 5 per group) at random, every group was received the following treatments: PBS, DOX, BPNs-PDA-
PEG/DOX, BPNs-PDA-PEG-PEITC/DOX, BPNs-PDA-PEG-PEITC +
3.22. Blood Sodiumfluoride analysis
Rats were separated into 2 groups randomly (each group n = 5): injected with BPNs-PDA-PEG-PEITC (3 mg/kg), and injected without BPNs-PDA-PEG-PEITC. Blood was collected after injection for 1 day, 7 days and 14 days. The serum biochemistry was tested by using the blood biochemistry analysis kits (JCBIO, China). Blood cell counts were tested using an automated blood cell counter (BC-2800 Vet Analyzers, China).
3.23. Statistical analysis
The analysis of variance (ANOVA) test was used to evaluate the significance of experimental results. Probabilities as p < 0.05 (*),
In summary, we have fabricated a BPNs-based multifunctional na-nocomposite for drug-resistant cancer multiple treatment. BPNs-PDA-PEG-PEITC possessed an extremely high drug loading capacity and pH/ NIR-responsive release properties. The presentence of PEITC could endow the nanocarrier with the capacity of depleting mutant p53 to enhance the DOX therapeutic effect on MCF-7/ADR cells. Besides, the introduction of Mn2+ ions give this nanoplatform great contrasts for MRI. BPNs-PDA-PEG-PEITC is an excellent photosensitizer to generate hyperthermia and ROS. Combining with those functions, MRI-guided PTT/PDT/chemo-therapy effectively inhibit drug-resistant tumor growth. This drug delivery system has a great application potential in the therapy of MDR cancer.
This project was supported by the Jiangsu six category outstanding talent (2012-NY-031), NJ-32, Jiangsu province science and technology support plan (BE2015367), Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, National and Local Joint Engineering Research Center of Biomedical Functional Materials and the Fundamental Research Funds for the Central Universities of Central South University (1053320182160). This work was also supported by the National Natural Science Foundation of China (No. 21705166).
Appendix A. Supplementary data
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