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 BYL-719 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
X. Zeng, L. Mei, TPGS-functionalized polydopamine-modified mesoporous silica as drug nanocarriers for enhanced lung cancer chemotherapy against nultidrug re-sistance, Small 13 (2017) 1700623.  L. Wang, X. Lin, J. Wang, Z. Hu, Y. Ji, S. Hou, Y. Zhao, X. Wu, C. Chen, Novel insights into combating cancer chemotherapy resistance using a plasmonic nano-carrier: enhancing drug sensitiveness and accumulation simultaneously with loca-lized mild photothermal stimulus of femtosecond pulsed laser, Adv. Funct. Mater. 24 (2014) 4229–4239.
 H. Wang, T. Maiyalagan, X. Wang, Review on recent progress in nitrogen-doped graphene: synthesis, characterization, and its potential applications, ACS Catal. 2 (2012) 781–794.
Y. Zhao, High-throughput synthesis of single-layer MoS2 nanosheets as a near-in-frared photothermal-triggered drug delivery for effective cancer therapy, ACS Nano 8 (2014) 6922–6933.
J. Lin, Integration of upconversion nanoparticles and ultrathin black phosphorus for efficient photodynamic theranostics under 808 nm near-infrared light irradiation, Chem. Mater. 28 (2016) 4724–4734.  C.X. Sun, L. Wen, J.F. Zeng, Y. Wang, Q. Sun, L.J. Deng, C.J. Zhao, Z. Li, One-pot solventless preparation of PEGylated black phosphorus nanoparticles for photo-acoustic imaging and photothermal therapy of cancer, Biomaterials 91 (2016) 81–89.
promising applications in energy, environmental, and biomedical fields, Chem. Rev.
 T. Liu, Y. Liu, Y. Chen, S.H. Liu, M.F. Maitz, X. Wang, Immobilization of heparin/ poly-L-lysine nanoparticles on dopamine-coated surface to create a heparin density gradient for selective direction of platelet and vascular cells behavior, Acta Biomater. 10 (2014) 1940–1954.
 M. Zhang, W.T. Wang, F. Wu, P. Yuan, C. Chi, N.L. Zhou, Magnetic and fluorescent carbon nanotubes for dual modal imaging and photothermal and chemo-therapy of cancer cells in living mice, Carbon 123 (2017) 70–83.  F. Wu, M. Zhang, H.W. Lu, D. Liang, Y.L. Huang, Y.H. Xia, Triple stimuli-responsive magnetic hollow porous carbon-based nanodrug delivery system for magnetic re-sonance imaging-guided synergistic photothermal/chemotherapy of cancer, ACS Appl. Mater. Interfaces 10 (2018) 21939–21949.