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Nano Research 2019, 12(4): 877-887 https://doi.org/10.1007/s12274-019-2318-7
Research Article | Issue | Published: 05 March 2019

Albumin-bound paclitaxel dimeric prodrug nanoparticles with tumor redox heterogeneity-triggered drug release for synergistic photothermal/chemotherapy

Show Author's Information Qing Pei1,2,  Xiuli Hu1( ),  Xiaohua Zheng1,2,  Rui Xia1,2,  Shi Liu1,  Zhigang Xie1( ),  Xiabin Jing1
State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry, Chinese Academy of Sciences,Changchun,130022,China;
University of Science and Technology of China,Hefei,230026,China;
Keywords:
human serum albumin, prodrug nanoparticles, tumor redox heterogeneity-responsiveness, controlled drug release, synergistic cancer therapy
Topics:
Biomimetics Chemotherapy DiseasesNanoparticlesTargeted drug deliveryTumors
Cite this article:
Pei Q, Hu X, Zheng X, et al. Albumin-bound paclitaxel dimeric prodrug nanoparticles with tumor redox heterogeneity-triggered drug release for synergistic photothermal/chemotherapy. Nano Research, 2019, 12(4): 877-887. https://doi.org/10.1007/s12274-019-2318-7
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Abstract Full text Electronic supplementary material About this article

Inspired by the clinically approved albumin based PTX formulation (Abraxane) and high-drug-loading dimeric prodrug tactics, herein we report a theranostic "Abraxane-like" prodrug formulation, which is comprised of human serum albumin (HSA), a paclitaxel (PTX) dimer bridged with thioether liner (PTX2-S), and photosensitizer IR780 iodide. Nanoparticles (NPs) with PTX2-S and IR780 as the core and HSA as the stealth shell are formed. Compared with HSA-based PTX clinical formulation (Abraxane), the dimeric molecules not only constitute the bulk structure of the particles, but also act as crossing agent, thus realizing drug loading content increasing from 6.6 wt.% to 48.7 wt.% with high loading efficiency (> 90%) and excellent stability in biological conditions. Importantly, the thioether linkage dually responds to the tumor redox heterogeneity and the NPs gradually releases the parent drug PTX for chemotherapy. Meanwhile, PTX2-S facilitates the encapsulation of IR780 iodide due to their π-π stacking interaction and IR780 iodide generates spatio-temporal hyperthermia under light irradiation to kill cancer cells for photothermal therapy. The described craft integrates the biomimetic trait of HSA, high drug loading, tumor redox heterogeneity- initiated on-demand drug release, and combination therapy into one formulation and the developed nanoparticles are promising for cancer treatment.


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Abstract
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Electronic supplementary material
About this article

Albumin-bound paclitaxel dimeric prodrug nanoparticles with tumor redox heterogeneity-triggered drug release for synergistic photothermal/chemotherapy

Show Author's information Qing Pei1,2, Xiuli Hu1( ), Xiaohua Zheng1,2, Rui Xia1,2, Shi Liu1, Zhigang Xie1( ), Xiabin Jing1
State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry, Chinese Academy of Sciences,Changchun,130022,China;
University of Science and Technology of China,Hefei,230026,China;

Abstract

Inspired by the clinically approved albumin based PTX formulation (Abraxane) and high-drug-loading dimeric prodrug tactics, herein we report a theranostic "Abraxane-like" prodrug formulation, which is comprised of human serum albumin (HSA), a paclitaxel (PTX) dimer bridged with thioether liner (PTX2-S), and photosensitizer IR780 iodide. Nanoparticles (NPs) with PTX2-S and IR780 as the core and HSA as the stealth shell are formed. Compared with HSA-based PTX clinical formulation (Abraxane), the dimeric molecules not only constitute the bulk structure of the particles, but also act as crossing agent, thus realizing drug loading content increasing from 6.6 wt.% to 48.7 wt.% with high loading efficiency (> 90%) and excellent stability in biological conditions. Importantly, the thioether linkage dually responds to the tumor redox heterogeneity and the NPs gradually releases the parent drug PTX for chemotherapy. Meanwhile, PTX2-S facilitates the encapsulation of IR780 iodide due to their π-π stacking interaction and IR780 iodide generates spatio-temporal hyperthermia under light irradiation to kill cancer cells for photothermal therapy. The described craft integrates the biomimetic trait of HSA, high drug loading, tumor redox heterogeneity- initiated on-demand drug release, and combination therapy into one formulation and the developed nanoparticles are promising for cancer treatment.

Keywords: human serum albumin, prodrug nanoparticles, tumor redox heterogeneity-responsiveness, controlled drug release, synergistic cancer therapy

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Publication history
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Acknowledgements

Publication history

Received: 21 November 2018
Revised: 25 January 2019
Accepted: 27 January 2019
Published: 05 March 2019
Issue date: April 2019

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 51773197 and 51522307).

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