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Research Article

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

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
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Graphical Abstract

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

intratumoral penetrationlight-responsivenesssinglet oxygen-degradable polymersize shrinkagecharge conversioniRGD

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Nano Research
Volume 13 Issue 10,
October 2020
Pages 2706-2715
DOI: 10.1007/s12274-020-2913-7
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
Topics:
Aliphatic compoundsMedical nanotechnologyNanoclustersTumors

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Received: 22 April 2020
Revised: 31 May 2020
Accepted: 03 June 2020
Published: 05 October 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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