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Nano Research 2020, 13(10): 2706-2715 https://doi.org/10.1007/s12274-020-2913-7
Research Article | Issue | Published: 05 October 2020

iRGD-reinforced, photo-transformable nanoclusters toward cooperative enhancement of intratumoral penetration and antitumor efficacy

Show Author's Information Jing Yan1,  Rongying Zhu2,  Fan Wu1,  Ziyin Zhao1,  Huan Ye1,  Mengying Hou1,  Yong Liu1( ),  Lichen Yin1( )
Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China
Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Keywords:
charge conversion, intratumoral penetration, light-responsiveness, singlet oxygen-degradable polymer, size shrinkage, iRGD
Topics:
Aliphatic compoundsMedical nanotechnologyNanoclustersTumors
Cite this article:
Yan J, Zhu R, Wu F, et al. iRGD-reinforced, photo-transformable nanoclusters toward cooperative enhancement of intratumoral penetration and antitumor efficacy. Nano Research, 2020, 13(10): 2706-2715. https://doi.org/10.1007/s12274-020-2913-7
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Abstract Full text Electronic supplementary material About this article

Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-responsive nanoclusters (NCs) capable of size shrinkage and charge conversion were developed and co-administered with iRGD to synergistically improve the intratumoral penetration and the anticancer efficacy. The NCs were constructed using the singlet oxygen-sensitive (SOS) polyethylene glycol- polyurethane-polyethylene glycol (PEG-(1O2)PU-PEG) triblock copolymer to encapsulate the doxorubicin (DOX)-loaded, chlorin e6 (Ce6)-conjugated polyamindoamine (PAMAM) dendrimer (DCD) via the double-emulsion method. Co-administration of iRGD notably increased the permeability of NCs within tumor vasculature and tumor tissues. In addition, upon far-red light irradiation (660 nm) of tumors at low optical density (10 mW/cm2), the generated 1O2 could disintegrate the NCs and release the DCD with positive surface charge and ultra-small size (~ 5 nm), which synergized with iRGD to enable deep intratumoral penetration. Consequently, the local 1O2 at lethal concentrations along with the released DOX efficiently and cooperatively eradicated tumor cells. This study provides a convenient approach to spatiotemporally promote the intratumoral penetration of nanomedicine and mediate programmed anticancer therapy.


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Electronic supplementary material
About this article

iRGD-reinforced, photo-transformable nanoclusters toward cooperative enhancement of intratumoral penetration and antitumor efficacy

Show Author's information Jing Yan1, Rongying Zhu2, Fan Wu1, Ziyin Zhao1, Huan Ye1, Mengying Hou1, Yong Liu1( ), Lichen Yin1( )
Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China
Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

Abstract

Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-responsive nanoclusters (NCs) capable of size shrinkage and charge conversion were developed and co-administered with iRGD to synergistically improve the intratumoral penetration and the anticancer efficacy. The NCs were constructed using the singlet oxygen-sensitive (SOS) polyethylene glycol- polyurethane-polyethylene glycol (PEG-(1O2)PU-PEG) triblock copolymer to encapsulate the doxorubicin (DOX)-loaded, chlorin e6 (Ce6)-conjugated polyamindoamine (PAMAM) dendrimer (DCD) via the double-emulsion method. Co-administration of iRGD notably increased the permeability of NCs within tumor vasculature and tumor tissues. In addition, upon far-red light irradiation (660 nm) of tumors at low optical density (10 mW/cm2), the generated 1O2 could disintegrate the NCs and release the DCD with positive surface charge and ultra-small size (~ 5 nm), which synergized with iRGD to enable deep intratumoral penetration. Consequently, the local 1O2 at lethal concentrations along with the released DOX efficiently and cooperatively eradicated tumor cells. This study provides a convenient approach to spatiotemporally promote the intratumoral penetration of nanomedicine and mediate programmed anticancer therapy.

Keywords: charge conversion, intratumoral penetration, light-responsiveness, singlet oxygen-degradable polymer, size shrinkage, iRGD

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Publication history
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Acknowledgements

Publication history

Received: 22 April 2020
Revised: 31 May 2020
Accepted: 03 June 2020
Published: 05 October 2020
Issue date: October 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

The research was financially supported by the National Natural Science Foundation of China (Nos. 51873142, 51722305, and 81903068), the Ministry of Science and Technology of China (No. 2016YFA0201200), 111 project, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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