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Nano Research 2014, 7(9): 1291-1301 https://doi.org/10.1007/s12274-014-0493-0
Research Article | Issue | Published: 30 July 2014

Gold nanorod-photosensitizer conjugate with extracellular pH-driven tumor targeting ability for photothermal/photodynamic therapy

Show Author's Information Nannan Wang1,§,  Zilong Zhao1,§,  Yifan Lv1,  Huanhuan Fan1,  Huarong Bai1,  Hongmin Meng1,  Yuqian Long1,  Ting Fu1,  Xiaobing Zhang1,  Weihong Tan1,2( )
Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Collaborative Research Center of Molecular Engineering for TheranosticsHunan UniversityChangsha410082China
Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at Bio/nano Interface, Shands Cancer CenterUF Genetics Institute and McKnight Brain Institute, University of FloridaGainesville, Florida32611-7200USA

§ These authors contributed equally to this work.

Keywords:
gold nanorods, photodynamic therapy, photothermal therapy, peptide, targeting acidity
Cite this article:
Wang N, Zhao Z, Lv Y, et al. Gold nanorod-photosensitizer conjugate with extracellular pH-driven tumor targeting ability for photothermal/photodynamic therapy. Nano Research, 2014, 7(9): 1291-1301. https://doi.org/10.1007/s12274-014-0493-0
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Abstract Full text Electronic supplementary material About this article

Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH (low) insertion peptide (pHLIP) with a disulfide bond which imparts extracellular pH (pHe)-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 (Ce6), a second-generation photosensitizer (PS), is used for photodynamic therapy (PDT). Gold nanorods (AuNRs) are used as a hyperthermia agent for photothermal therapy (PTT) and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pHe-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6-pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPss-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione (GSH), and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention (EPR) effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.


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Electronic supplementary material
About this article

Gold nanorod-photosensitizer conjugate with extracellular pH-driven tumor targeting ability for photothermal/photodynamic therapy

Show Author's information Nannan Wang1,§, Zilong Zhao1,§, Yifan Lv1, Huanhuan Fan1, Huarong Bai1, Hongmin Meng1, Yuqian Long1, Ting Fu1, Xiaobing Zhang1, Weihong Tan1,2( )
Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Collaborative Research Center of Molecular Engineering for TheranosticsHunan UniversityChangsha410082China
Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at Bio/nano Interface, Shands Cancer CenterUF Genetics Institute and McKnight Brain Institute, University of FloridaGainesville, Florida32611-7200USA

§ These authors contributed equally to this work.

Abstract

Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH (low) insertion peptide (pHLIP) with a disulfide bond which imparts extracellular pH (pHe)-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 (Ce6), a second-generation photosensitizer (PS), is used for photodynamic therapy (PDT). Gold nanorods (AuNRs) are used as a hyperthermia agent for photothermal therapy (PTT) and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pHe-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6-pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPss-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione (GSH), and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention (EPR) effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.

Keywords: gold nanorods, photodynamic therapy, photothermal therapy, peptide, targeting acidity

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Acknowledgements

Publication history

Received: 31 January 2014
Revised: 01 May 2014
Accepted: 05 May 2014
Published: 30 July 2014
Issue date: September 2014

Copyright

© Tsinghua University Press and Springer‐Verlag Berlin Heidelberg 2014

Acknowledgements

Acknowledgements

This work is supported by grants awarded by the National Institutes of Health (GM079359 and CA133086), by the National Key Scientific Program of China (2011CB911000), NSFC grants (NSFC 21221003 and NSFC 21327009) and China National Instrumentation Program 2011YQ03012412.

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