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Nano Research 2023, 16(1): 980-990 https://doi.org/10.1007/s12274-022-4819-z
Research Article | Issue | Published: 26 August 2022

Modularly engineered prodrug-nanoassemblies for cancer therapy: Nonpharmacological moiety dominating delivery fates

Show Author's Information Yuequan Wang1,  Qian Qiu1,  Rui Liao1,  Xinhui Wang1,  Ziran Zhou1,  Xuanbo Zhang1,  Haotian Zhang2,  Zhonggui He1,  Shenwu Zhang1( ),  Cong Luo1( ),  Jin Sun1( )
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
Keywords:
paclitaxel, small-molecule prodrug, self-assembly ability, nonpharmacological moiety, modular engineering, delivery fate
Topics:
Drug delivery
Cite this article:
Wang Y, Qiu Q, Liao R, et al. Modularly engineered prodrug-nanoassemblies for cancer therapy: Nonpharmacological moiety dominating delivery fates. Nano Research, 2023, 16(1): 980-990. https://doi.org/10.1007/s12274-022-4819-z
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Abstract Full text Electronic supplementary material About this article

Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment. Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability, tumor-specific prodrug activation, and satisfactory antitumor effect. However, too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties. Herein, we found that iso-carbon fatty acids with different number, position, and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies. Particularly, the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs, but also exert significant influences on the pharmacokinetics, prodrug activation, and antitumor activity of prodrug-nanoassemblies. Finally, oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrug-nanoassemblies. This study elucidates the crucial roles of nonpharmacological moieties in prodrugs, and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy.


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Electronic supplementary material
About this article

Modularly engineered prodrug-nanoassemblies for cancer therapy: Nonpharmacological moiety dominating delivery fates

Show Author's information Yuequan Wang1, Qian Qiu1, Rui Liao1, Xinhui Wang1, Ziran Zhou1, Xuanbo Zhang1, Haotian Zhang2, Zhonggui He1, Shenwu Zhang1( ), Cong Luo1( ), Jin Sun1( )
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China

Abstract

Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment. Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability, tumor-specific prodrug activation, and satisfactory antitumor effect. However, too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties. Herein, we found that iso-carbon fatty acids with different number, position, and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies. Particularly, the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs, but also exert significant influences on the pharmacokinetics, prodrug activation, and antitumor activity of prodrug-nanoassemblies. Finally, oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrug-nanoassemblies. This study elucidates the crucial roles of nonpharmacological moieties in prodrugs, and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy.

Keywords: paclitaxel, small-molecule prodrug, self-assembly ability, nonpharmacological moiety, modular engineering, delivery fate

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Publication history
Copyright
Acknowledgements

Publication history

Received: 28 June 2022
Revised: 20 July 2022
Accepted: 25 July 2022
Published: 26 August 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was financially supported by Shenyang Youth Science and Technology Innovation Talents Program (No. RC210452), the Liaoning Revitalization Talents Program (No. XLYC1907129), the Excellent Youth Science Foundation of Liaoning Province (No. 2020-YQ-06), and the China Postdoctoral Science Foundation (Nos. 2020M670794 and 2021MD703858).

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