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Synthesis of doxorubicin pro-drug nanoparticles based on poloxamer188 and studies on their in vivo bio-security and in vitro anti-tumor activities

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Abstract

The purpose of this study was to develop a novel glutathione (GSH)-responsible doxorubicin (DOX) pro-drug (poloxamer188-S-S-DOX, PSSD) nanoparticles and study on their in vitro anti-tumor activity. The PSSD pro-drug was synthesized by conjugating DOX molecules onto poloxamer188 chains with disulfide bonds as linkers. The PSSD nanoparticles (NPs) were fabricated by a solvent-evaporation method, and the in vitro anti-4T1 cell activity and in vivo bio-security of PSSD NPs were investigated. The proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR) spectra confirmed the synthesis of PSSD pro-drug. The results from transmission electron microscopy (TEM) and nano-ZS90 dynamic light scattering (DLS) showed that these mono-dispersed PSSD NPs were round-shaped with a diameter of 117.4 ± 0.8 nm. Bio-security studies found that the PSSD NPs did not induce obvious toxicity toward administrated Kunming mice. Furthermore, the PSSD NPs could be taken in by 4T1cells. In tumor cells, the disulfide bonds cleaved by the reducing action of GSH and the conjugated DOX were released. Therefore, the PSSD pro-drug improved the in vitro anti-tumor activity of free DOX molecules.

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The relevant data supporting this study’s findings are available on reasonable request from the corresponding authors.

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Acknowledgements

This work was financed by the Scientific & Technological Projects of Henan Province (Grant No. 222102310415) and the Natural Science Foundation of Henan Province (232300420020).

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Authors and Affiliations

  1. College of Pharmacy, Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China

    Yongli Shi, Xueyan Hou, Sha Sha Yu, Xiaofei Pan, Mingbo Yang, Jie Hu & Xiao Wang

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Correspondence to Yongli Shi.

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Shi, Y., Hou, X., Yu, S.S. et al. Synthesis of doxorubicin pro-drug nanoparticles based on poloxamer188 and studies on their in vivo bio-security and in vitro anti-tumor activities. Iran Polym J 33, 481–492 (2024). https://doi.org/10.1007/s13726-023-01267-5

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