Colorectal Tumor Microenvironment-Activated Bio-Decomposable and Metabolizable Cu2 O@CaCO3 Nanocomposites for Synergistic Oncotherapy.

Chang, M; Hou, Z; Jin, D; Zhou, J; Wang, M; Wang, M; Shu, M; Ding, B; Li, C; Lin, J

Colorectal Tumor Microenvironment-Activated Bio-Decomposable and Metabolizable Cu2 O@CaCO3 Nanocomposites for Synergistic Oncotherapy.

Chang, M Hou, Z Jin, D

Zhou, J

Wang, M Wang, M Shu, M Ding, B Li, C Lin, J

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Advanced Materials, 2020, 32, (43), pp. 1-11
Issue Date:: 2020-10

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Field	Value	Language
dc.contributor.author	Chang, M
dc.contributor.author	Hou, Z
dc.contributor.author	Jin, D https://orcid.org/0000-0003-1046-2666
dc.contributor.author	Zhou, J https://orcid.org/0000-0002-0605-5745
dc.contributor.author	Wang, M
dc.contributor.author	Wang, M
dc.contributor.author	Shu, M
dc.contributor.author	Ding, B
dc.contributor.author	Li, C
dc.contributor.author	Lin, J
dc.date.accessioned	2020-11-11T02:55:39Z
dc.date.available	2020-11-11T02:55:39Z
dc.date.issued	2020-10
dc.identifier.citation	Advanced Materials, 2020, 32, (43), pp. 1-11
dc.identifier.issn	0935-9648
dc.identifier.issn	1521-4095
dc.identifier.uri	http://hdl.handle.net/10453/143891
dc.description.abstract	Rational design of tumor microenvironment (TME)-activated nanocomposites provides an innovative strategy to construct responsive oncotherapy. In colorectal cancer (CRC), the specific physiological features are the overexpressed endogenous H2 S and slightly acidic microenvironment. Here, a core-shell Cu2 O@CaCO3 nanostructure for CRC "turn-on" therapy is reported. With CaCO3 responsive to pH decomposition and Cu2 O responsive to H2 S sulfuration, Cu2 O@CaCO3 can be triggered "on" into the therapeutic mode by the colorectal TME. When the CaCO3 shell decomposes and releases calcium in acidic colorectal TME, the loss of protection from the CaCO3 shell exposes the Cu2 O core to be sulfuretted by H2 S to form metabolizable Cu31 S16 nanocrystals that gain remarkably strong near-infrared absorption. After modifying hyaluronic acid, Cu2 O@CaCO3 can achieve synergistic CRC-targeted and TME-triggered photothermal/photodynamic/chemodynamic/calcium-overload-mediated therapy. Moreover, it is found that the generation of hyperthermia and oxidative stress from Cu2 O@CaCO3 nanocomposites can efficiently reprogram the macrophages from the M2 phenotype to the M1 phenotype and initiate a vaccine-like immune effect after primary tumor removal, which further induces an immune-favorable TME and intense immune responses for anti-CD47 antibody to simultaneously inhibit CRC distant metastasis and recurrence by immunotherapy.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Advanced Materials
dc.relation.isbasedon	10.1002/adma.202004647
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	02 Physical Sciences, 03 Chemical Sciences, 09 Engineering
dc.subject.classification	Nanoscience & Nanotechnology
dc.title	Colorectal Tumor Microenvironment-Activated Bio-Decomposable and Metabolizable Cu2 O@CaCO3 Nanocomposites for Synergistic Oncotherapy.
dc.type	Journal Article
utslib.citation.volume	32
utslib.location.activity	Germany
utslib.for	02 Physical Sciences
utslib.for	03 Chemical Sciences
utslib.for	09 Engineering
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
pubs.consider-herdc	true
dc.date.updated	2020-11-11T02:55:34Z
pubs.issue	43
pubs.publication-status	Published
pubs.volume	32
utslib.citation.issue	43

Abstract:

Rational design of tumor microenvironment (TME)-activated nanocomposites provides an innovative strategy to construct responsive oncotherapy. In colorectal cancer (CRC), the specific physiological features are the overexpressed endogenous H2 S and slightly acidic microenvironment. Here, a core-shell Cu2 O@CaCO3 nanostructure for CRC "turn-on" therapy is reported. With CaCO3 responsive to pH decomposition and Cu2 O responsive to H2 S sulfuration, Cu2 O@CaCO3 can be triggered "on" into the therapeutic mode by the colorectal TME. When the CaCO3 shell decomposes and releases calcium in acidic colorectal TME, the loss of protection from the CaCO3 shell exposes the Cu2 O core to be sulfuretted by H2 S to form metabolizable Cu31 S16 nanocrystals that gain remarkably strong near-infrared absorption. After modifying hyaluronic acid, Cu2 O@CaCO3 can achieve synergistic CRC-targeted and TME-triggered photothermal/photodynamic/chemodynamic/calcium-overload-mediated therapy. Moreover, it is found that the generation of hyperthermia and oxidative stress from Cu2 O@CaCO3 nanocomposites can efficiently reprogram the macrophages from the M2 phenotype to the M1 phenotype and initiate a vaccine-like immune effect after primary tumor removal, which further induces an immune-favorable TME and intense immune responses for anti-CD47 antibody to simultaneously inhibit CRC distant metastasis and recurrence by immunotherapy.

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http://hdl.handle.net/10453/143891