NIR-light-controlled G-quadruplex hydrogel for synergistically enhancing photodynamic therapy via sustained delivery of metformin and catalase-like activity in breast cancer

Yanting Sun; Kang Fang; Xiaochun Hu; Jingxian Yang; Zhengyang Jiang; Lei Feng; Ruihao Li; Yiming Rao; Shuo Shi; Chunyan Dong

Materials Today Bio (Dec 2022)

NIR-light-controlled G-quadruplex hydrogel for synergistically enhancing photodynamic therapy via sustained delivery of metformin and catalase-like activity in breast cancer

Yanting Sun,
Kang Fang,
Xiaochun Hu,
Jingxian Yang,
Zhengyang Jiang,
Lei Feng,
Ruihao Li,
Yiming Rao,
Shuo Shi,
Chunyan Dong

Affiliations

Yanting Sun: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Kang Fang: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Xiaochun Hu: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Jingxian Yang: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Zhengyang Jiang: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Lei Feng: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Ruihao Li: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Yiming Rao: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China
Shuo Shi: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China; Corresponding author.
Chunyan Dong: Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, PR China; Corresponding author.

Journal volume & issue: Vol. 16
p. 100375

Abstract

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Severely hypoxic condition of tumour represents a notable obstacle against the efficiency of photodynamic therapy (PDT). While mitochondria targeted therapy by metformin has been considered as a promising strategy for reducing oxygen consumption in tumours, its low treatment sensitivity, short half-life and narrow absorption window in vivo remain the intractable challenges. In this report, 5′-guanosine monophosphate (5′GMP), indocyanine green (ICG), hemin and metformin, were combined to construct a smart G-quadruplex (G4) hydrogel named HMI@GEL for breast cancer (BC) treatment. Benefiting from the photothermal (PTT) effect of ICG, HMI@GEL exhibited excellent characteristics of NIR-light-triggered and persistent drug delivery to maintain high intratumoral concentration of metformin. Furthermore, drug loading concentration of metformin reached an amazing 300 mg mL−1 in HMI@GEL. To our knowledge, it might be the highest loading efficiency in the reported literatures. With the combination of catalase-mimicking Hemin@mil88, metformin could inhibit tumour mitochondrial respiratory significantly, which sequentially permitted in situ efficient oxygen generation. Remarkable apoptosis and necrosis were achieved by the combination of PTT and synergistically enhanced PDT as well as the activated tumour immunotherapy. Collectively, the HMI@GEL in situ injectable platform showed a promising strategy for enhanced PDT by metformin, and opened new perspectives for treating BC versatilely.

Published in Materials Today Bio

ISSN: 2590-0064 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.journals.elsevier.com/materials-today-bio

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