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  • br Conclusions br In summary our study provides proof

    2020-03-24


    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.
    Acknowledgments
    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
    References
    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, https://doi.org/10.1016/j.apsb.2019.03.006
    + MODEL
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