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Nano Research

Article Title

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

Authors

Jing Yan, 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
Rongying Zhu, Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Fan Wu, 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
Ziyin Zhao, 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
Huan Ye, 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
Mengying Hou, 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
Yong Liu, 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
Lichen Yin, 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

Keywords

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

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 glycolpolyurethane-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.

Graphical Abstract

Publisher

Tsinghua University Press

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