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Article ; Online: AIEgens Cross-linked Iron Oxide Nanoparticles Synchronously Amplify Bimodal Imaging Signals in Situ by Tumor Acidity-Mediated Click Reaction.

Dong, Yansong / Liu, Ye / Tu, Yalan / Yuan, Youyong / Wang, Jun

Angewandte Chemie (International ed. in English)

2023 Volume 62, Issue 52, Page(s) e202310975

Abstract: Activatable dual-modal molecular imaging probes present a promising tool for the diagnosis of malignant tumors. However, synchronously enhancing dual-modal imaging signals under a single stimulus is challenging. Herein, we propose an activatable bimodal ... ...

Abstract	Activatable dual-modal molecular imaging probes present a promising tool for the diagnosis of malignant tumors. However, synchronously enhancing dual-modal imaging signals under a single stimulus is challenging. Herein, we propose an activatable bimodal probe that integrates aggregation-induced emission luminogens (AIEgens) and iron oxide nanoparticles (IOs) to synergistically enhance near-infrared fluorescence (NIRF) intensity and magnetic resonance (MR) contrast through a tumor acidity-mediated click reaction. Tumor acidity-responsive IOs containing dibenzocyclooctyne groups (termed cDIOs) and AIEgens containing azide groups (termed AATs) can be covalently cross-linked in response to tumor acidity, which leads to a simultaneous enhancement in NIRF intensity (≈12.4-fold) and r
MeSH term(s)	Mice ; Animals ; Neoplasms ; Molecular Probes ; Magnetic Resonance Imaging/methods ; Molecular Imaging ; Magnetic Iron Oxide Nanoparticles ; Nanoparticles ; Optical Imaging/methods
Chemical Substances	Molecular Probes
Language	English
Publishing date	2023-11-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202310975
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Article ; Online: Bioorthogonal chemistry and illumination controlled programmed size-changeable nanomedicine for synergistic photodynamic and hypoxia-activated therapy.

Jiang, Maolin / Liu, Ye / Dong, Yansong / Wang, Kewei / Yuan, Youyong

Biomaterials

2022 Volume 284, Page(s) 121480

Abstract: Photodynamic therapy (PDT) can aggravate the hypoxia aggravation and be further utilized for the activation of hypoxia-activated prodrug (HAP). Ideally, photosensitizers (PSs) are mainly administrated to tumor vasculatures adjacent to regions with high ... ...

Abstract	Photodynamic therapy (PDT) can aggravate the hypoxia aggravation and be further utilized for the activation of hypoxia-activated prodrug (HAP). Ideally, photosensitizers (PSs) are mainly administrated to tumor vasculatures adjacent to regions with high oxygen to effectively generate reactive oxygen species (ROS) effectively and further aggravate tumor hypoxia, while the HAP is delivered to the inner tumor as far as possible for efficient activation. However, a delivery system capable of transporting PSs and HAP to the desired region respectively for the optimum effect is urgently needed. Here, we developed a bioorthogonal click chemistry and illumination controlled programmed size-changeable nanomedicine for synergistic photodynamic and hypoxia-activated therapy. It utilized tumor acidity responsive bioorthogonal click reaction for crosslinking nanoparticles to construct a drug depot with tumor vasculatures adjacent region retention for PDT in normoxia. Under laser illumination, cleavage of the ROS-responsive thioketal (TK) crosslinker to release small sized poly(amidoamine) (PAMAM) dendrimer conjugated with HAP for enhanced tumor penetration into the hypoxic region. Therefore, this strategy could differentially deliver PSs and HAP in desired spatial distribution, eventually achieving the enhanced synergistic enhancement in the combined PDT and hypoxia-activated therapy.
MeSH term(s)	Cell Line, Tumor ; Humans ; Hypoxia/drug therapy ; Lighting ; Nanomedicine ; Nanoparticles/therapeutic use ; Photochemotherapy ; Photosensitizing Agents/therapeutic use ; Prodrugs/therapeutic use ; Reactive Oxygen Species
Chemical Substances	Photosensitizing Agents ; Prodrugs ; Reactive Oxygen Species
Language	English
Publishing date	2022-04-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121480
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Article: Cinnamaldehyde-based poly(thioacetal): A ROS-awakened self-amplifying degradable polymer for enhanced cancer immunotherapy

Tu, Yalan / Xiao, Xuan / Dong, Yansong / Li, Jisi / Liu, Ye / Zong, Qingyu / Yuan, Youyong

Biomaterials. 2022 Oct., v. 289

2022

Abstract: Although stimuli-responsive polymers have emerged as promising strategies for intelligent cancer therapy, limited polymer degradation and insufficient drug release remain a challenge. Here, we report a novel reactive oxygen species (ROS)-awakened self- ... ...

Abstract	Although stimuli-responsive polymers have emerged as promising strategies for intelligent cancer therapy, limited polymer degradation and insufficient drug release remain a challenge. Here, we report a novel reactive oxygen species (ROS)-awakened self-amplifying degradable cinnamaldehyde (CA)-based poly(thioacetal) polymer. The polymer consists of ROS responsive thioacetal (TA) group and CA as the ROS generation agent. The self-amplified polymer degradation process is triggered by endogenous ROS-induced cleavage of the TA group to release CA. The CA released then promotes the generation of more ROS through mitochondrial dysfunction, resulting in amplified polymer degradation. More importantly, poly(thioacetal) itself can trigger immunogenic cell death (ICD) of the tumor cells and its side chains can be conjugated with indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor to reverse the immunosuppressive tumor microenvironment for synergistic cancer immunotherapy. The self-amplified degradable poly(thioacetal) developed in this work provides insights into the development of novel stimulus-responsive polymers for enhanced cancer immunotherapy.
Keywords	biocompatible materials ; cancer therapy ; cell death ; drugs ; immunosuppression ; immunotherapy ; indoleamine 2,3-dioxygenase ; mitochondria ; neoplasms ; polymers ; reactive oxygen species
Language	English
Dates of publication	2022-10
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121795
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Article: Bioorthogonal chemistry and illumination controlled programmed size-changeable nanomedicine for synergistic photodynamic and hypoxia-activated therapy

Jiang, Maolin / Liu, Ye / Dong, Yansong / Wang, Kewei / Yuan, Youyong

Biomaterials. 2022 May, v. 284

2022

Abstract	Photodynamic therapy (PDT) can aggravate the hypoxia aggravation and be further utilized for the activation of hypoxia-activated prodrug (HAP). Ideally, photosensitizers (PSs) are mainly administrated to tumor vasculatures adjacent to regions with high oxygen to effectively generate reactive oxygen species (ROS) effectively and further aggravate tumor hypoxia, while the HAP is delivered to the inner tumor as far as possible for efficient activation. However, a delivery system capable of transporting PSs and HAP to the desired region respectively for the optimum effect is urgently needed. Here, we developed a bioorthogonal click chemistry and illumination controlled programmed size-changeable nanomedicine for synergistic photodynamic and hypoxia-activated therapy. It utilized tumor acidity responsive bioorthogonal click reaction for crosslinking nanoparticles to construct a drug depot with tumor vasculatures adjacent region retention for PDT in normoxia. Under laser illumination, cleavage of the ROS-responsive thioketal (TK) crosslinker to release small sized poly(amidoamine) (PAMAM) dendrimer conjugated with HAP for enhanced tumor penetration into the hypoxic region. Therefore, this strategy could differentially deliver PSs and HAP in desired spatial distribution, eventually achieving the enhanced synergistic enhancement in the combined PDT and hypoxia-activated therapy.
Keywords	acidity ; biocompatible materials ; chemical reactions ; crosslinking ; dendrimers ; hypoxia ; lighting ; nanomedicine ; neoplasms ; normoxia ; oxygen ; photochemotherapy ; reactive oxygen species
Language	English
Dates of publication	2022-05
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121480
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Article ; Online: microRNA-132 inhibits the proliferation, migration, and invasion of ovarian cancer cells by regulating CT10 oncogenic gene homolog II-related signaling pathways.

Jiang, Haiyan / Dai, Min / Wu, Yao / Dong, Yansong / Qi, Lei / Xi, Qinghua / Liang, Guiwen

Translational cancer research

2022 Volume 9, Issue 7, Page(s) 4433–4443

Abstract: Background: Despite a large amount of evidence showing the involvement of microRNA-132 (miR-132) in the occurrence and prognosis of many different types of cancer, the role of miR-132 in ovarian cancer and its potential molecular mechanism have yet to ... ...

Abstract	Background: Despite a large amount of evidence showing the involvement of microRNA-132 (miR-132) in the occurrence and prognosis of many different types of cancer, the role of miR-132 in ovarian cancer and its potential molecular mechanism have yet to be fully explained. Method: We studied the biological function and molecular mechanism of miR-132 in ovarian cancer cell lines and clinical tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, Luciferase reporter assay, CCK8 test, colony formation test, and scratch and Transwell assays. Results: The expression level of miR-132 was significantly reduced in ovarian cancer cell lines and clinical tissue samples. When the level of miR-132 was increased, the proliferation, colony-forming, migration, and invasion abilities of ovarian cancer cells were significantly inhibited. We found that miR-132 inhibits the expression of transcription factor CT10 Oncogenic Gene Homologue II (CRKII) through specific targeting of mRNA 3'-UTR. We also observed a significant increase in CRKII expression in ovarian cancer. Notably, CRKII expression was negatively correlated with miR-132 expression in clinical ovarian cancer tissue. Down-regulation of CRKII had a similar inhibitory effect on miR-132 overexpression in ovarian cancer cells, while excessive expression of CRKII reversed the inhibitory effect mediated by the excessive expression of miR-132. Conclusions: miR-132 inhibits the proliferation, invasion, and migration abilities of ovarian cancer cells through targeting CRKII.
Language	English
Publishing date	2022-01-20
Publishing country	China
Document type	Journal Article
ZDB-ID	2901601-0
ISSN	2219-6803 ; 2218-676X
ISSN (online)	2219-6803
ISSN	2218-676X
DOI	10.21037/tcr-20-2435
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Article ; Online: Cinnamaldehyde-based poly(thioacetal): A ROS-awakened self-amplifying degradable polymer for enhanced cancer immunotherapy.

Tu, Yalan / Xiao, Xuan / Dong, Yansong / Li, Jisi / Liu, Ye / Zong, Qingyu / Yuan, Youyong

Biomaterials

2022 Volume 289, Page(s) 121795

Abstract	Although stimuli-responsive polymers have emerged as promising strategies for intelligent cancer therapy, limited polymer degradation and insufficient drug release remain a challenge. Here, we report a novel reactive oxygen species (ROS)-awakened self-amplifying degradable cinnamaldehyde (CA)-based poly(thioacetal) polymer. The polymer consists of ROS responsive thioacetal (TA) group and CA as the ROS generation agent. The self-amplified polymer degradation process is triggered by endogenous ROS-induced cleavage of the TA group to release CA. The CA released then promotes the generation of more ROS through mitochondrial dysfunction, resulting in amplified polymer degradation. More importantly, poly(thioacetal) itself can trigger immunogenic cell death (ICD) of the tumor cells and its side chains can be conjugated with indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor to reverse the immunosuppressive tumor microenvironment for synergistic cancer immunotherapy. The self-amplified degradable poly(thioacetal) developed in this work provides insights into the development of novel stimulus-responsive polymers for enhanced cancer immunotherapy.
MeSH term(s)	Acrolein/analogs & derivatives ; Cell Line, Tumor ; Humans ; Immunotherapy ; Indoleamine-Pyrrole 2,3,-Dioxygenase/therapeutic use ; Nanoparticles/chemistry ; Neoplasms/drug therapy ; Polymers/chemistry ; Reactive Oxygen Species/metabolism ; Stimuli Responsive Polymers ; Tumor Microenvironment
Chemical Substances	Indoleamine-Pyrrole 2,3,-Dioxygenase ; Polymers ; Reactive Oxygen Species ; Stimuli Responsive Polymers ; Acrolein (7864XYD3JJ) ; cinnamaldehyde (SR60A3XG0F)
Language	English
Publishing date	2022-09-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121795
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Article ; Online: Polyprodrug with glutathione depletion and cascade drug activation for multi-drug resistance reversal.

Xiao, Xuan / Wang, Kewei / Zong, Qingyu / Tu, Yalan / Dong, Yansong / Yuan, Youyong

Biomaterials

2021 Volume 270, Page(s) 120649

Abstract: High intracellular glutathione (GSH) levels play an important role in multidrug resistance (MDR) in cancer cells. It remains challenging to develop a drug delivery system that is simultaneously capable of GSH depletion and drug activation for multidrug ... ...

Abstract	High intracellular glutathione (GSH) levels play an important role in multidrug resistance (MDR) in cancer cells. It remains challenging to develop a drug delivery system that is simultaneously capable of GSH depletion and drug activation for multidrug resistance reversal. Herein, we designed a polyprodrug (denoted as PSSD) based on poly(disulfide) conjugated with doxorubicin (DOX) on the polymer side chains that exhibits GSH depletion and cascade DOX activation for drug resistance reversal. The poly(disulfide) backbone with a high disulfide density depletes intracellular antioxidant GSH via the disulfide-thiol exchange reaction to disrupt intracellular redox homeostasis in cells. Simultaneously, DOX can be activated through a cascade reaction, and degradation of the poly(disulfide) backbone further facilitates its drug release. Therefore, poly(disulfide) can be used as a GSH scavenger to reverse MDR as well as a prodrug backbone to target high intracellular GSH levels in cancer cells, providing a general strategy for drug resistance reversal.
MeSH term(s)	Activation, Metabolic ; Doxorubicin/pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Glutathione/metabolism
Chemical Substances	Doxorubicin (80168379AG) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2021-01-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2020.120649
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Article: AIEgen based drug delivery systems for cancer therapy

Dong, Yansong / Bin Liu / Youyong Yuan

Journal of controlled release. 2018 Nov. 28, v. 290

2018

Abstract: Fluorescent drug delivery systems provide a means to track drug release, trace processes of translocation, monitor excretion of anticancer agents and predict therapeutic responses. Traditional fluorescent dye-labeled drug delivery systems often suffer ... ...

Abstract	Fluorescent drug delivery systems provide a means to track drug release, trace processes of translocation, monitor excretion of anticancer agents and predict therapeutic responses. Traditional fluorescent dye-labeled drug delivery systems often suffer from notorious aggregation-caused quenching (ACQ) with greatly impeded imaging performance. The emerging fluorogens with aggregation-induced emission characteristics (AIEgens) have provided an elegant alternative to tackle this challenge. Recently, fluorescent drug delivery systems based on AIEgens which combine fluorescence imaging and drug delivery have been extensively studied for the development of theranostic nanomedicine. In this review, we summarize the recent development of fluorescent drug delivery systems using AIEgens as the signal reporter. This review is organized according to the drug delivery systems, which include: (1) AIEgens as the drug delivery carrier; (2) AIE polymer as the drug delivery carrier; (3) Organic-inorganic AIE nanocarrier for drug delivery; (4) Supramolecular AIE system for drug delivery. Through illustration of their design principles and application examples, we hope to stimulate more interest in the design of more advanced fluorescent drug delivery systems based on AIEgens for cancer therapy.
Keywords	antineoplastic agents ; excretion ; fluorescence ; image analysis ; nanocarriers ; nanomedicine ; neoplasms ; polymers
Language	English
Dates of publication	2018-1128
Size	p. 129-137.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2018.09.028
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Article: Intercellular delivery of bioorthogonal chemical receptors for enhanced tumor targeting and penetration

Tu, Yalan / Dong, Yansong / Wang, Kewei / Shen, Song / Yuan, Youyong / Wang, Jun

Biomaterials. 2020 Nov., v. 259

2020

Abstract: Targeted drug delivery using biological ligands can improve the precision of cancer therapy. However, this active targeting strategy is limited in tumor targeting and penetration abilities due to the paucity and heterogeneous distribution of targeted ... ...

Abstract	Targeted drug delivery using biological ligands can improve the precision of cancer therapy. However, this active targeting strategy is limited in tumor targeting and penetration abilities due to the paucity and heterogeneous distribution of targeted receptors in tumor cells, thus compromising the treatment outcomes. In this study, we developed an alternative active targeting strategy for enhanced tumor targeting and penetration through synthetic nanoparticle-mediated metabolic tumor ligand labeling for intercellular delivery of bioorthogonal chemical receptors combined with in vivo bioorthogonal click chemistry. Briefly, artificial azide-containing ligands were first labeled on perivascular tumor cells by nanoscale metabolic precursors (Az-NPs) via the enhanced permeability and retention (EPR) effect and metabolic engineering of the tumor cells. Through transport by extracellular vesicles (EVs) secreted by perivascular tumor cells, the azide-containing ligands can be autonomously transported intercellularly to adjacent cells and further spread throughout tumor tissues and label bioorthogonal ligands on cells that are not in proximity to blood vessels. Then, water-soluble dibenzocyclooctyne-modified chlorin e6 (DBCO-Ce6) was intravenously injected to react selectively, efficiently and irreversibly with the azide groups on the cell surface through an in vivo bioorthogonal click reaction. Enhanced tumor accumulation and penetration of DBCO-Ce6 was achieved through this strategy, resulting in improved therapeutic efficiency with laser irradiation for photodynamic therapy. Therefore, the artificial azide-containing ligand targeting strategy by nanoparticle-mediated metabolic labeling through the EPR effect combined with bioorthogonal click chemistry may provide an alternative strategy for enhanced tumor targeting and penetration with broad applications.
Keywords	azides ; biocompatible materials ; cancer therapy ; chlorins ; drugs ; intravenous injection ; irradiation ; ligands ; neoplasms ; permeability ; photochemotherapy ; water solubility
Language	English
Dates of publication	2020-11
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2020.120298
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Article ; Online: AIEgen based drug delivery systems for cancer therapy.

Dong, Yansong / Liu, Bin / Yuan, Youyong

Journal of controlled release : official journal of the Controlled Release Society

2018 Volume 290, Page(s) 129–137

Abstract	Fluorescent drug delivery systems provide a means to track drug release, trace processes of translocation, monitor excretion of anticancer agents and predict therapeutic responses. Traditional fluorescent dye-labeled drug delivery systems often suffer from notorious aggregation-caused quenching (ACQ) with greatly impeded imaging performance. The emerging fluorogens with aggregation-induced emission characteristics (AIEgens) have provided an elegant alternative to tackle this challenge. Recently, fluorescent drug delivery systems based on AIEgens which combine fluorescence imaging and drug delivery have been extensively studied for the development of theranostic nanomedicine. In this review, we summarize the recent development of fluorescent drug delivery systems using AIEgens as the signal reporter. This review is organized according to the drug delivery systems, which include: (1) AIEgens as the drug delivery carrier; (2) AIE polymer as the drug delivery carrier; (3) Organic-inorganic AIE nanocarrier for drug delivery; (4) Supramolecular AIE system for drug delivery. Through illustration of their design principles and application examples, we hope to stimulate more interest in the design of more advanced fluorescent drug delivery systems based on AIEgens for cancer therapy.
MeSH term(s)	Animals ; Diagnostic Imaging ; Drug Delivery Systems ; Fluorescent Dyes/administration & dosage ; Humans ; Neoplasms/diagnostic imaging ; Neoplasms/drug therapy ; Polymers/administration & dosage ; Theranostic Nanomedicine
Chemical Substances	Fluorescent Dyes ; Polymers
Language	English
Publishing date	2018-10-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2018.09.028
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