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Dual-stimuli-sensitive poly(ortho ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy

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Abstract

Herein, new poly(ortho ester disulfide urethanes) (POEDU) and poly(ortho ester urethanes) (POEU) were successfully synthesized via polycondensation between active esters of 1,6-hexandiol (HD) and dual-stimuli-sensitive ortho ester disulfide diamine or pH-senstive ortho ester diamine. The corresponding POEDU and POEU nanospheres were easily fabricated using an oil-in-water emulsion technique. In vitro degradation experiments indicated that POEDU nanospheres degraded faster than POEU nanospheres in mildly acidic and reductive environments. Doxorubicin (DOX) as a model antitumor drug was successfully incorporated into these nanospheres to give DOX-loaded nanoparticles (POEDU-DOX and POEU-DOX). In vitro drug release studies showed that release of DOX from dual-stimuli-sensitive POEDU-DOX was accelerated compared with release from the pH-sensitive POEU-DOX under DL-dithiothreitol (DTT) and mildly acidic conditions. In addition, in vitro uptake and cytotoxicity assays revealed that POEDU-DOX exhibited more efficient antitumor effect than POEU-DOX did against both two-dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS). Finally, in a mice H22 tumor model, POEDU-DOX exhibited preferable antitumor capability. In conclusion, the pH and redox dual-stimuli-sensitive POEDU nanospheres can be superior drug carriers for cancer treatment.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51503001, 51603001), the Research Foundation for Key Program of Education Department of Anhui Province of China (KJ2016A030), the Doctor Research Foundation of Anhui University (J10113190075), and the Academic and Technology Introduction Project of Anhui University (AU02303203).

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Authors and Affiliations

  1. Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Science, Anhui University, Hefei, 230601, China

    Yan Huang, Jiejie Qin, Jun Wang, Guoqing Yan, Xin Wang & Rupei Tang

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  1. Yan Huang
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  2. Jiejie Qin
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  3. Jun Wang
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  4. Guoqing Yan
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  5. Xin Wang
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  6. Rupei Tang
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Correspondence to Rupei Tang.

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11426_2018_9269_MOESM1_ESM.doc

Dual-stimuli-sensitive poly(ortho ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy

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Huang, Y., Qin, J., Wang, J. et al. Dual-stimuli-sensitive poly(ortho ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy. Sci. China Chem. 61, 1447–1459 (2018). https://doi.org/10.1007/s11426-018-9269-6

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