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Nano Research 2024, 17(6): 5491-5500 https://doi.org/10.1007/s12274-024-6533-5
Research Article | Issue | Published: 29 February 2024

Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs

Show Author's Information Yuanhao Yu1,§,  Shiyi Zuo2,§,  Jiaxuan Song2,§,  Lingxiao Li2,  Tian Liu2,  Jiayu Guo2,  Yaqiao Li2,  Danping Wang1,  Qi Lu2,  Helin Wang2,  Dun Zhou3,  Zhonggui He2,  Xiaohong Liu1( ),  Bingjun Sun2,4( ),  Jin Sun2,4( )
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China
Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang 110016, China

§ Yuanhao Yu, Shiyi Zuo, and Jiaxuan Song contributed equally to this work.

Keywords:
albumin, doxorubicin, nanomedicines, fatty acid prodrug, pH-sensitive bond
Topics:
Drug delivery
An erratum to this article is available online at https://doi.org/10.1007/s12274-024-6611-8
Cite this article:
Yu Y, Zuo S, Song J, et al. Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs. Nano Research, 2024, 17(6): 5491-5500. https://doi.org/10.1007/s12274-024-6533-5
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Abstract Full text Electronic supplementary material About this article

Albumin nanoparticles (ANPs) offer unique advantages for antitumor drug delivery system, including non-immunogenicity and inherent tumor-targeting capacity. At present, only a few products, such as ABRAXANE® and FYARRO™, have been approved for clinical applications. The poor affinity of doxorubicin (DOX) for albumin, coupled with its numerous severe adverse reactions, poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX. In this study, we developed prodrugs by conjugating fatty acids of varying lengths with DOX. Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules. We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs. Compared to free DOX, all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm. Additionally, DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells. Significantly, the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids, impacting their in vivo pharmacokinetics, antitumor effectiveness and tumor accumulation. This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs, and it builds a good platform for creating ANPs which prioritize high drug loading, high efficiency, and minimal side effects.


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Abstract
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Electronic supplementary material
About this article

Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs

Show Author's information Yuanhao Yu1,§, Shiyi Zuo2,§, Jiaxuan Song2,§, Lingxiao Li2, Tian Liu2, Jiayu Guo2, Yaqiao Li2, Danping Wang1, Qi Lu2, Helin Wang2, Dun Zhou3, Zhonggui He2, Xiaohong Liu1( ), Bingjun Sun2,4( ), Jin Sun2,4( )
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China
Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang 110016, China

§ Yuanhao Yu, Shiyi Zuo, and Jiaxuan Song contributed equally to this work.

Abstract

Albumin nanoparticles (ANPs) offer unique advantages for antitumor drug delivery system, including non-immunogenicity and inherent tumor-targeting capacity. At present, only a few products, such as ABRAXANE® and FYARRO™, have been approved for clinical applications. The poor affinity of doxorubicin (DOX) for albumin, coupled with its numerous severe adverse reactions, poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX. In this study, we developed prodrugs by conjugating fatty acids of varying lengths with DOX. Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules. We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs. Compared to free DOX, all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm. Additionally, DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells. Significantly, the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids, impacting their in vivo pharmacokinetics, antitumor effectiveness and tumor accumulation. This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs, and it builds a good platform for creating ANPs which prioritize high drug loading, high efficiency, and minimal side effects.

Keywords: albumin, doxorubicin, nanomedicines, fatty acid prodrug, pH-sensitive bond

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Publication history
Copyright
Acknowledgements

Publication history

Received: 10 November 2023
Revised: 30 January 2024
Accepted: 31 January 2024
Published: 29 February 2024
Issue date: June 2024

Copyright

© Tsinghua University Press, corrected publication 2024

Acknowledgements

Acknowledgements

This work was financially supported by the National Key R&D Program of China (No. 2022YFE0111600), National Natural Science Foundation of China (Nos. 82272151 and 82204318).

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