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  • br Conclusions br In summary our study provides proof


    4. Conclusions
    In summary, our study provides proof-of-concept for 7pep-M-RAP as a novel treatment modality to improve the therapeutic efficacy of chemotherapeutic nanomedicine. 7pep-M-RAP revealed synergistic anti-tumor effect with cytotoxic 7pep-M-PTX on MCF-7 breast cancer. Through ligand‒receptor-mediated active targeting and inducing massive accumulation of autophagic vesicles, combination chemotherapy that acted on both ACD and apoptosis provided
    enhanced efficacy and reduced toxicity. Combined with targeted DDS (7pep-M-PTX) of chemotherapeutic agent, 7pep-M-RAP brought on mitochondria-associated apoptosis and direct tumor suppression. To the best of our knowledge, relevant studies have not reported previ-ously that RAP is prepared as a targeting DDS for inducing ACD. As a result, the combination of autophagy-targeted DDS with cytotoxicity-targeted DDS provided superior therapeutic efficacy by increasing tumor tissue accumulation and enhancing cellular uptake, with low myelosuppression and systemic toxicity. We speculate that the combined strategy of targeting autophagic cell death may be a promising approach for the effective treatment of breast cancer by modulating autophagy and regulating apoptosis, so as to be extended to numerous tumor models with several other nanosystems.
    This research was supported by the National Natural Science Foundation of China (81690264), Key Project from the Ministry of Science and Technology (Grant No. 2018ZX09721003), Sci-entific Research Incubation Fund of Beijing Children’s Hospital, Capital Medical University (Grant No. GPY201711, China).
    Appendix A. Supplementary data
    Please cite this Okadaic acid article as: Mei D et al., Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer, Acta Pharmaceutica Sinica B,
    + MODEL
    3. Yano S, Takeuchi S, Nakagawa T, Yamada T. Ligand-triggered resistance to molecular targeted drugs in lung cancer: roles of hepa-tocyte growth factor and epidermal growth factor receptor ligands. Cancer Sci 2012;103:1189e94.
    4. Qin SY, Cheng YJ, Lei Q, Zhang AQ, Zhang XZ. Combinational strategy for high-performance cancer chemotherapy. Biomaterials 2018;171:178e97.
    5. Liu Q, Qian Y, Li P, Zhang S, Wang Z, Liu J, et al. The combined therapeutic effects of 131iodine-labeled multifunctional copper sulfide-loaded microspheres in treating breast cancer. Acta Pharm Sin B 2018; 8:371e80.
    6. Tian F, Dahmani FZ, Qiao J, Ni J, Xiong H, Liu T, et al. A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer. Acta Biomater 2018;75:398e412.
    7. Yap TA, Omlin A, de Bono JS. Development of therapeutic combi-nations targeting major cancer signaling pathways. J Clin Oncol 2013; 31:1592e605.
    and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2þ advanced breast cancer in BOLERO-1. Breast Cancer Res 2017;19:47.
    10. Jovanovic B, Mayer IA, Mayer EL, Abramson VG, Bardia A, Sanders ME, et al. A randomized phase II neoadjuvant study of cisplatin, paclitaxel with or without everolimus in patients with stage II/III triple-negative breast cancer (TNBC): responses and long-term outcome correlated with increased frequency of DNA damage response gene mutations, TNBC subtype, AR status, and Ki67. Clin Cancer Res 2017;23:4035e45.
    11. Beck JT, Mantooth R. A case of disease improvement after treatment with everolimus plus exemestane in a patient with hormone receptor-positive metastatic breast cancer with bone metastases. Case Rep Oncol 2015;8:101e5.
    12. Andre´ F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2014; 15:580e91.