Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies

Multifunctional nanomedicine has offered a promising strategy for effective anticancer therapy owing to its versatile capabilities. However, the systematic precise delivery still remains intractable challenge because of the existence of multi-staged biological barriers after intravenous administrati...

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Main Authors: Pengcheng Hu, Wenjun Wang, Jingyun Sha, Yujuan Xing, Yong Wang, Changyu Wu, Jingjing Li, Kai Gao, Haicui Dong, Shaohui Zheng
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Materials & Design
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0264127522010528
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author Pengcheng Hu
Wenjun Wang
Jingyun Sha
Yujuan Xing
Yong Wang
Changyu Wu
Jingjing Li
Kai Gao
Haicui Dong
Shaohui Zheng
author_facet Pengcheng Hu
Wenjun Wang
Jingyun Sha
Yujuan Xing
Yong Wang
Changyu Wu
Jingjing Li
Kai Gao
Haicui Dong
Shaohui Zheng
author_sort Pengcheng Hu
collection DOAJ
description Multifunctional nanomedicine has offered a promising strategy for effective anticancer therapy owing to its versatile capabilities. However, the systematic precise delivery still remains intractable challenge because of the existence of multi-staged biological barriers after intravenous administration. Herein, to address this issue, injectable and TME-responsive nanocomposite hydrogels were developed for localized and synergistic cancer therapy. The nanocomposite hydrogels (Au NBPs&Pt NCs@DOX gel) were synthesized via the formation of metal-sulfur bonds between 4arm-PEG-thiol and Au nanobipyramids or Pt nanoclusters with the DOX encapsulation. The hydrogel exhibited rapid gelation and excellent injectability. Attributed to the high absorbance of Au NBPs, the nanocomposite hydrogels revealed superior photothermal effect under NIR irradiation, which the DOX release was also regulated by NIR laser. In addition, the catalase- and peroxidase-like activities of Pt NCs were validated to convert endogenous H2O2 into ROS and O2 in situ to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Simultaneously, catalytic therapy combined with NIR irradiation exhibited strongest inhibition to the growth of 4T1 tumor in vitro and in vivo. Thus, this study provided a new strategy for TME remodeling and local combination therapies of different therapeutic agents.
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spelling doaj.art-fd01318092ea428ba823d1875ea297c42023-01-30T04:11:44ZengElsevierMaterials & Design0264-12752023-01-01225111429Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapiesPengcheng Hu0Wenjun Wang1Jingyun Sha2Yujuan Xing3Yong Wang4Changyu Wu5Jingjing Li6Kai Gao7Haicui Dong8Shaohui Zheng9School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, ChinaDepartment of Orthopedics, Jining No. 1 People's Hospital, Jining, Shandong 272002, China; Corresponding authors.Department of Cardiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, China; Corresponding authors.School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Corresponding authors.Multifunctional nanomedicine has offered a promising strategy for effective anticancer therapy owing to its versatile capabilities. However, the systematic precise delivery still remains intractable challenge because of the existence of multi-staged biological barriers after intravenous administration. Herein, to address this issue, injectable and TME-responsive nanocomposite hydrogels were developed for localized and synergistic cancer therapy. The nanocomposite hydrogels (Au NBPs&Pt NCs@DOX gel) were synthesized via the formation of metal-sulfur bonds between 4arm-PEG-thiol and Au nanobipyramids or Pt nanoclusters with the DOX encapsulation. The hydrogel exhibited rapid gelation and excellent injectability. Attributed to the high absorbance of Au NBPs, the nanocomposite hydrogels revealed superior photothermal effect under NIR irradiation, which the DOX release was also regulated by NIR laser. In addition, the catalase- and peroxidase-like activities of Pt NCs were validated to convert endogenous H2O2 into ROS and O2 in situ to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Simultaneously, catalytic therapy combined with NIR irradiation exhibited strongest inhibition to the growth of 4T1 tumor in vitro and in vivo. Thus, this study provided a new strategy for TME remodeling and local combination therapies of different therapeutic agents.http://www.sciencedirect.com/science/article/pii/S0264127522010528Au nanobipyramidsNanocomposite hydrogelNanozymetic activityTME modulationSynergistic therapy
spellingShingle Pengcheng Hu
Wenjun Wang
Jingyun Sha
Yujuan Xing
Yong Wang
Changyu Wu
Jingjing Li
Kai Gao
Haicui Dong
Shaohui Zheng
Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies
Materials & Design
Au nanobipyramids
Nanocomposite hydrogel
Nanozymetic activity
TME modulation
Synergistic therapy
title Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies
title_full Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies
title_fullStr Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies
title_full_unstemmed Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies
title_short Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies
title_sort tumor microenvironment responsive multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo photothermal therapies
topic Au nanobipyramids
Nanocomposite hydrogel
Nanozymetic activity
TME modulation
Synergistic therapy
url http://www.sciencedirect.com/science/article/pii/S0264127522010528
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