Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma

Osteosarcoma (OS) is one of the most common malignant tumors in children and young adults. As chemotherapy and other therapies are limited by low therapeutic efficiency, severe side effects and single therapeutic function, it is of high value to develop innovative therapies for precise and efficient...

Full description

Bibliographic Details
Main Authors: Feng Liang, Xueying An, Ruoxi Wang, Wenshu Wu, Lin Yang, Yixin Zheng, Qing Jiang, Xingquan Xu, Danni Zhong, Min Zhou
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-06-01
Series:Engineered Regeneration
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666138124000161
_version_ 1827223444295516160
author Feng Liang
Xueying An
Ruoxi Wang
Wenshu Wu
Lin Yang
Yixin Zheng
Qing Jiang
Xingquan Xu
Danni Zhong
Min Zhou
author_facet Feng Liang
Xueying An
Ruoxi Wang
Wenshu Wu
Lin Yang
Yixin Zheng
Qing Jiang
Xingquan Xu
Danni Zhong
Min Zhou
author_sort Feng Liang
collection DOAJ
description Osteosarcoma (OS) is one of the most common malignant tumors in children and young adults. As chemotherapy and other therapies are limited by low therapeutic efficiency, severe side effects and single therapeutic function, it is of high value to develop innovative therapies for precise and efficient treatment of OS. Herein, natural photosynthetic microalgae (C. vulgaris, CV) were utilized as carriers for the chemotherapeutic agent doxorubicin (DOX) to create a multifunctional therapeutic platform (CV@DOX) for the photo-modulation of the tumor microenvironment (TME) and synergistic chemo-photodynamic therapy of osteosarcoma. CV@DOX exhibited rapid drug release behavior in the acidic TME, improving the efficiency of chemotherapy against tumors and reducing side effects on other normal tissues. Under 650 nm laser irradiation, CV@DOX demonstrated the ability to effectively generate oxygen to alleviate tumor hypoxia and utilize the photosensitizing properties of chlorophyll in CV to produce an increased amount of reactive oxygen species (ROS), thereby enhancing photodynamic therapy (PDT). CV@DOX-mediated synergistic chemo-photodynamic therapy demonstrated efficacy in halting tumor progression in an orthotopic osteosarcoma mouse model by promoting tumor cell apoptosis, inhibiting tumor proliferation and angiogenesis. Moreover, chlorophyll-assisted fluorescence imaging enabled monitoring of the distribution of CV@DOX in osteosarcoma after administration. Finally, CV@DOX did not cause significant hematological and tissue toxicity, and prevented DOX-induced cardiotoxicity, showing good in vivo biocompatibility. Overall, this work presents a novel TME-responsive and TME-modulating platform for imaging-guided multimodal osteosarcoma treatment.
first_indexed 2024-04-24T11:37:36Z
format Article
id doaj.art-bc78b4aeb1cf4dbcae67219dc32da80b
institution Directory Open Access Journal
issn 2666-1381
language English
last_indexed 2025-03-21T16:54:29Z
publishDate 2024-06-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Engineered Regeneration
spelling doaj.art-bc78b4aeb1cf4dbcae67219dc32da80b2024-06-15T06:13:06ZengKeAi Communications Co., Ltd.Engineered Regeneration2666-13812024-06-0152199209Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcomaFeng Liang0Xueying An1Ruoxi Wang2Wenshu Wu3Lin Yang4Yixin Zheng5Qing Jiang6Xingquan Xu7Danni Zhong8Min Zhou9Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, PR China; Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, PR ChinaState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR ChinaInstitute of Translational Medicine, Zhejiang University, Hangzhou, 310029, PR ChinaState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR ChinaState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, PR ChinaState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR China; Corresponding authors.State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR China; Corresponding authors.Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029, PR China; Corresponding authors.Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, PR China; Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining, 314400, PR China; Zhejiang University-Ordos City Etuoke Banner Joint Research Center, Zhejiang University, Haining, 314400, PR China; Corresponding authors.Osteosarcoma (OS) is one of the most common malignant tumors in children and young adults. As chemotherapy and other therapies are limited by low therapeutic efficiency, severe side effects and single therapeutic function, it is of high value to develop innovative therapies for precise and efficient treatment of OS. Herein, natural photosynthetic microalgae (C. vulgaris, CV) were utilized as carriers for the chemotherapeutic agent doxorubicin (DOX) to create a multifunctional therapeutic platform (CV@DOX) for the photo-modulation of the tumor microenvironment (TME) and synergistic chemo-photodynamic therapy of osteosarcoma. CV@DOX exhibited rapid drug release behavior in the acidic TME, improving the efficiency of chemotherapy against tumors and reducing side effects on other normal tissues. Under 650 nm laser irradiation, CV@DOX demonstrated the ability to effectively generate oxygen to alleviate tumor hypoxia and utilize the photosensitizing properties of chlorophyll in CV to produce an increased amount of reactive oxygen species (ROS), thereby enhancing photodynamic therapy (PDT). CV@DOX-mediated synergistic chemo-photodynamic therapy demonstrated efficacy in halting tumor progression in an orthotopic osteosarcoma mouse model by promoting tumor cell apoptosis, inhibiting tumor proliferation and angiogenesis. Moreover, chlorophyll-assisted fluorescence imaging enabled monitoring of the distribution of CV@DOX in osteosarcoma after administration. Finally, CV@DOX did not cause significant hematological and tissue toxicity, and prevented DOX-induced cardiotoxicity, showing good in vivo biocompatibility. Overall, this work presents a novel TME-responsive and TME-modulating platform for imaging-guided multimodal osteosarcoma treatment.http://www.sciencedirect.com/science/article/pii/S2666138124000161OsteosarcomaTumor hypoxiaPhotodynamicChemotherapySynergistic therapy
spellingShingle Feng Liang
Xueying An
Ruoxi Wang
Wenshu Wu
Lin Yang
Yixin Zheng
Qing Jiang
Xingquan Xu
Danni Zhong
Min Zhou
Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma
Engineered Regeneration
Osteosarcoma
Tumor hypoxia
Photodynamic
Chemotherapy
Synergistic therapy
title Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma
title_full Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma
title_fullStr Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma
title_full_unstemmed Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma
title_short Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma
title_sort microalgae based drug delivery system for tumor microenvironment photo modulating and synergistic chemo photodynamic therapy of osteosarcoma
topic Osteosarcoma
Tumor hypoxia
Photodynamic
Chemotherapy
Synergistic therapy
url http://www.sciencedirect.com/science/article/pii/S2666138124000161
work_keys_str_mv AT fengliang microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT xueyingan microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT ruoxiwang microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT wenshuwu microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT linyang microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT yixinzheng microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT qingjiang microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT xingquanxu microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT dannizhong microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma
AT minzhou microalgaebaseddrugdeliverysystemfortumormicroenvironmentphotomodulatingandsynergisticchemophotodynamictherapyofosteosarcoma