Intratibial osteosarcoma growth and pulmonary metastasis inhibition by HIPPO signaling pathway-induced photodynamic therapy

Wenyi Wang; Junli Chang; Hongfeng Ruan; Xingyuan Sun; Fulai Zhao; Peng Zhao; Chujie Zhou; Junjie Tong; Suxia Guo; Qi Shi; Yongjun Wang; Weian Zhang; Yanping Yang

Materials & Design (Sep 2023)

Intratibial osteosarcoma growth and pulmonary metastasis inhibition by HIPPO signaling pathway-induced photodynamic therapy

Wenyi Wang,
Junli Chang,
Hongfeng Ruan,
Xingyuan Sun,
Fulai Zhao,
Peng Zhao,
Chujie Zhou,
Junjie Tong,
Suxia Guo,
Qi Shi,
Yongjun Wang,
Weian Zhang,
Yanping Yang

Affiliations

Wenyi Wang: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Junli Chang: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Hongfeng Ruan: Institute of Orthopaedic and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310053, Zhejiang, China
Xingyuan Sun: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Fulai Zhao: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Peng Zhao: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Chujie Zhou: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Junjie Tong: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Suxia Guo: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Qi Shi: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China
Yongjun Wang: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China; Corresponding authors at: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Weian Zhang: Shanghai Key Laboratory of Advanced Polymeric Materials, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China; Corresponding authors at: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Yanping Yang: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, China; Corresponding authors at: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Journal volume & issue: Vol. 233
p. 112269

Abstract

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Cancer is a global leading cause of death, with nearly 10 million people dying from cancer in 2020. Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, the potential molecular mechanisms remain obscure. Herein, we designed a near-infrared (NIR) light-activated nanoplatform (TPBC-PEG) to explore the therapeutic effects and mechanisms of PDT by using a model of intratibial primary and pulmonary metastasis osteosarcoma. Under laser irradiation, TPBC-PEG photosensitizer dose-dependently inhibited proliferative and metastatic capabilities while promoting apoptosis of osteosarcoma cells in vitro, and also effectively suppressed carcinogenesis and pulmonary metastasis in osteosarcoma xenograft mouse model. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis after high-throughput mRNA-seq indicated that the HIPPO signaling pathway was one of the 20 most significantly related signaling pathways. And a series of experiments for determining the HIPPO signaling activity were conducted to reconfirm the specificity. Collectively, PDT of TPBC-PEG micelles against carcinogenesis and pulmonary metastasis of deep-seated intratibial osteosarcoma was achieved by activating HIPPO signaling pathway. Our study identified a hitherto uncharacterized molecular mechanism of PDT, which may provide new insights to understand and design promising nanoplatforms for future cancer therapies.

Published in Materials & Design

ISSN: 0264-1275 (Print); 1873-4197 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials
Website: https://www.journals.elsevier.com/materials-and-design

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