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Nano Research 2019, 12(11): 2815-2826 https://doi.org/10.1007/s12274-019-2518-1
Research Article | Issue | Published: 27 September 2019

Dual pH-responsive "charge-reversal like" gold nanoparticles to enhance tumor retention for chemo-radiotherapy

Show Author's Information Xiaolei Zhang1,§,  Chuangnian Zhang2,§,  Mingbo Cheng1,  Yahui Zhang1,  Wei Wang1,  Zhi Yuan1( )
Key Laboratory of Functional Polymer Materials of the Ministry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin300071China
Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical EngineeringChinese Academy of Medical Science & Peking Union Medical CollegeTianjin300192China

§Xiaolei Zhang and Chuangnian Zhang contributed equally to this work.

Keywords:
pH-responsive, aggregation, charge-reversal, enhanced retention, radiosentisizers
Topics:
Cell death Drug deliveryDrug dosage Gold nanoparticlesNanoparticlesTumorsX-rays
Cite this article:
Zhang X, Zhang C, Cheng M, et al. Dual pH-responsive "charge-reversal like" gold nanoparticles to enhance tumor retention for chemo-radiotherapy. Nano Research, 2019, 12(11): 2815-2826. https://doi.org/10.1007/s12274-019-2518-1
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Abstract Full text Electronic supplementary material About this article

The strategy of pH-responsive aggregation in tumor micro-environment (TME) provides an intriguing platform for enhancing tumor retention and exerting therapeutic effects sufficiently. In this work, we have designed an intelligent dual pH-responsive self-aggregating nano gold system (Au@PAH-Pt/DMMA) for the combined chemo-radiotherapy, in which a "charge-reversal like" strategy was utilized to realize irreversible stable aggregation and pH-specific release of cisplatin prodrug in TME. Responsive aggregation increases the cellular uptake of Au@PAH-Pt/DMMA by 55%–60%, and the cellular uptake of Pt after X-ray irradiation can be further enhanced by 80%. Additionally, responsive aggregation greatly slows down the rate of efflux from tumor in vivo. This system not only promotes B16 cell apoptosis as a chemotherapeutic agent (30.4%), it also enhances the effect of chemo-radiotheray (CRT) by promoting apoptosis as a radiosensitizer (55.3%). The colony formation assay results were fitted to cell survival curve of B16 cells and the sensitization enhancement ratio (SER) was calculated to be 1.29, which shows a good radiosensitizing ability. When exposed to X-ray, this nanoplatform reached the ideal therapeutic effect, and the tumor inhibition rate of Au@PAH-Pt/DMMA reached 91.6% with low drug administration frequency and dose of X-ray. Overall, the dual pH-responsive nanoparticles Au@PAH-Pt/DMMA could effectively enhance tumor therapeutic efficiency by combined chemo-radiotherapy, which provides a potential method for clinical transformation of cancer treatment.


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About this article

Dual pH-responsive "charge-reversal like" gold nanoparticles to enhance tumor retention for chemo-radiotherapy

Show Author's information Xiaolei Zhang1,§, Chuangnian Zhang2,§, Mingbo Cheng1, Yahui Zhang1, Wei Wang1, Zhi Yuan1( )
Key Laboratory of Functional Polymer Materials of the Ministry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin300071China
Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical EngineeringChinese Academy of Medical Science & Peking Union Medical CollegeTianjin300192China

§Xiaolei Zhang and Chuangnian Zhang contributed equally to this work.

Abstract

The strategy of pH-responsive aggregation in tumor micro-environment (TME) provides an intriguing platform for enhancing tumor retention and exerting therapeutic effects sufficiently. In this work, we have designed an intelligent dual pH-responsive self-aggregating nano gold system (Au@PAH-Pt/DMMA) for the combined chemo-radiotherapy, in which a "charge-reversal like" strategy was utilized to realize irreversible stable aggregation and pH-specific release of cisplatin prodrug in TME. Responsive aggregation increases the cellular uptake of Au@PAH-Pt/DMMA by 55%–60%, and the cellular uptake of Pt after X-ray irradiation can be further enhanced by 80%. Additionally, responsive aggregation greatly slows down the rate of efflux from tumor in vivo. This system not only promotes B16 cell apoptosis as a chemotherapeutic agent (30.4%), it also enhances the effect of chemo-radiotheray (CRT) by promoting apoptosis as a radiosensitizer (55.3%). The colony formation assay results were fitted to cell survival curve of B16 cells and the sensitization enhancement ratio (SER) was calculated to be 1.29, which shows a good radiosensitizing ability. When exposed to X-ray, this nanoplatform reached the ideal therapeutic effect, and the tumor inhibition rate of Au@PAH-Pt/DMMA reached 91.6% with low drug administration frequency and dose of X-ray. Overall, the dual pH-responsive nanoparticles Au@PAH-Pt/DMMA could effectively enhance tumor therapeutic efficiency by combined chemo-radiotherapy, which provides a potential method for clinical transformation of cancer treatment.

Keywords: pH-responsive, aggregation, charge-reversal, enhanced retention, radiosentisizers

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Publication history
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Acknowledgements

Publication history

Received: 29 June 2019
Revised: 12 September 2019
Accepted: 14 September 2019
Published: 27 September 2019
Issue date: November 2019

Copyright

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

Acknowledgements

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Nos. 51433004, 51773096, and 21604095); Natural Science Foundation of Tianjin (Nos. 17JCZDJC33500 and 18JCQNJC14500); Program for Innovative Research Team in Peking Union Medical College, CAMS Initiative for Innovative Medicine (No. 2017-I2M-3-022); Specific Program for High-Tech Leader & Team of Tianjin Government, Tianjin innovation and promotion plan key innovation team of immunoreactive biomaterials. We would like to thank Qiang Wu for FTIR spectroscopy and the guidance, Zhiqing Qiao and Lei Chen for ICP-OES, Yujun Yan and Jie Gu for radiotherapy experiments, Yajuan Wan and Rui Wang for flow cytometry, and Mengyue Pei for in vitro experiments.

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