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H2O2响应
BIOMATERIALS · 2019 · IF 10.273

H2O2-responsive biodegradable nanomedicine for cancer-selective dual-modal imaging guided precise photodynamic therapy

Qin Zeng,Ruijing Zhang,Tao Zhang,Da Xing

A tumor-related stimuli-activatable and biodegradable nanoplatform for tumor-selective imaging and effective photodynamic therapy (PDT) towards precision medicine is highly desirable but still greatly challenging. Here, we developed a novel H 2 O 2 -activatable and biodegradable nanomedicine (BSA-MBPB) by encapsulation of a single newly synthesized pro-photosensitizer (MBPB) with its photoactivity completely annihilated within bovine serum albumin (BSA) to achieve imaging-guided tumor-targeted effective PDT. BSA-MBPB can be decomposed and activated by H 2 O 2 to not only produce the clinical photosensitizer methylene blue to recover its fluorescent, photoacoustic and photosensitizing properties for dual-modal imaging and cytotoxic singlet oxygen ( 1 O 2 ) generation, but also to simultaneously produce a GSH-depleting adjuvant quinone methide to boost the 1 O 2 yield, thus strengthening the efficacy of PDT. BSA-MBPB allows for highly efficient and accurate PDT without major side effects, offering potential as the next-generation nanomedicine towards clinical practice of precise PDT.

研究领域: 肿瘤学 · 纳米医学 · 生物材料科学
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Advanced Science · 2019 ·Vol. 6 ·期 20 ·1901461 · IF 15.804

Right Cu2−xS@MnS Core–Shell Nanoparticles as a Photo/H2O2-Responsive Platform for Effective Cancer Theranostics

Xiaojuan Huang,Guoying Deng,Yong Han,Guizhu Yang,Rujia Zou,Zhiyuan Zhang,Shuyang Sun,Junqing Hu

Stimuli-responsive nanomedicines have become a recent research focus as a candidate for cancer treatment because of their effectiveness, sensibility, and minimal invasiveness. In this work, a novel nanosystem is developed based on Cu 2− x S@MnS core–shell nanoparticles (CSNPs) in which the Cu 2− x S core serves as a photosensitizer to generate hyperthermia and reactive oxygen species (ROS), and the MnS shell is used in H 2 O 2 -responsive O 2 production. Cu 2 −x S@MnS CSNPs with an independent core and shell ratio are synthesized by a controllable hot-injection method, resulting in an optimal photothermal (PT) effect with a PT conversion efficiency of up to 47.9%. An enhanced photodynamic (PD) effect also occurs in an H 2 O 2 environment. More significantly, in vivo experiments demonstrate that Cu 2 −x S@MnS CSNPs can mediate tumor shrinkage in both HeLa tumor cell line-derived xenograft (CDX) and head and neck squamous cell carcinoma (HNSCC) patient-derived xenograft (PDX) models, with the capability of being used as a T1-enhanced magnetic resonance (MR) contrast agent. These results suggest the great potential of as-prepared Cu 2 −x S@MnS CSNPs as photo/H 2 O 2 -responsive therapeutic-agents against tumors, even in a complicated and heterogeneous environment, thus promoting the clinical translation of nanomedicine.

CAS / MDL: 112-55-0 112-90-3
研究领域: 生物医学工程 · 纳米医学 · 癌症治疗
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Nanoscale · 2023 · IF 6.7

ICAM-1 targeted and ROS-responsive nanoparticles for the treatment of acute lung injury

Yu Ran,Shanmei Yin,Pei Xie,Yaxue Liu,ying wang,Zongning Yin

Acute Lung Injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target to the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). In vitro, Dex/PSB-γ3 NPs had rapid H2O2 responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.

研究领域: 药理学 · 纳米技术 · 炎症 · 呼吸医学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

H2O2-Responsive Gold Nanoclusters @ Mesoporous Silica @ Manganese Dioxide Nanozyme for “Off/On” Modulation and Enhancement of Magnetic Resonance Imaging and Photodynamic Therapy

Zhibin Yin,Qian Ji,Di Wu,Ziwei Li,Minfei Fan,Hongxin Zhang,Xiaolong Zhao,Aiguo Wu,Liang Cheng,Leyong Zeng

In order to achieve safe and high-efficient photodynamic therapy (PDT), it was a powerful strategy of constructing O2-generated nanozyme with intelligent “off/on” modulation and enhancement. Herein, a kind of H2O2-responsive nanozyme was developed for off/on modulation and enhancement of magnetic resonance (MR) imaging and PDT, in which great amounts of gold nanoclusters (AuNCs) were loaded into mesoporous silica to form nanoassembly, and manganese dioxide (MnO2) nanosheets were wrapped as switching shield shell (AuNCs@mSiO2@MnO2). In a neutral physiological environment, stable MnO2 shells eliminated singlet oxygen (1O2) generation to switch off PDT and MR imaging. However, in an acidic tumor microenvironment, the MnO2 shell reacted with H2O2, in which MnO2 degradation switched on MR imaging and PDT, and the generated O2 further enhanced PDT. H2O2-responsive MnO2 degradation brought about excellent MR imaging with a longitudinal relaxation rate of 25.31 mM–1 s–1, and simultaneously sufficient O2 generation guaranteed a 74% high 1O2 yield. Under the irradiation of a 635 nm laser, the viability of MDA-MB-435 cells was reduced to 4%, and the tumors completely disappeared, demonstrating strong PDT performance. Therefore, H2O2-responsive AuNCs@mSiO2@MnO2 nanozyme showed excellent off/on modulation and enhancement of MR imaging and PDT and was a promising intelligent nanoprobe for safe and high-efficiency theranostics.

研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 材料科学 · 诊疗学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

A simple yet effective hydrogel dressing for advanced microenvironmental management of diabetic wounds with intrinsic regulation

Kun Liu,Yu Kang,Xianzhen Dong,Qianyun Li,Yue Wang,Xiaopei Wu,Xiaofan Yang,Zhenbing Chen,Honglian Dai

Diabetic wounds are challenging to heal due to high glucose levels, and oxidative stress, impaired immune response and delayed angiogenesis. Hydrogel dressings capable of adapting and improving multiple microenvironments have broad prospects for application in clinical diabetes wound healing. In this study, we developed a photocrosslinked chitosan hydrogel using the antioxidant molecule “lipoic acid”, eliminating the need for additional photoinitiators. The obtained hydrogel exhibited respectable adhesion (adhesion strengths to iron, wood and skin are 0.045 MPa, 0.049 MPa and 0.041 MPa, respectively), photo-induced self-healing, and responsiveness to pH, H 2 O 2 and glucose. Notably, as compared to conventional injectable methacrylated chitosan hydrogel, LAMC hydrogels displayed the abilities to regulate the wound environment, such as reducing oxidative stress, blood sugar levels, and pH, and creating a favorable microenvironment for wound healing. Exosome-loaded LAMC hydrogels enabled targeted exosome release based on glucose concentration, pH, and H 2 O 2 to promote angiogenesis and accelerate healing. Our study offers a novel method for preparing injectable chitosan hydrogels and introduces a new strategy for developing drug-delivery systems that effectively promote diabetic wound healing, potentially transforming current therapeutic approaches.

研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 药学
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ACS Nano · 2019 · IF 13.903

Differential Diagnosis and Precision Therapy of Two Typical Malignant Cutaneous Tumors Leveraging Their Tumor Microenvironment: A Photomedicine Strategy

Peiru Wang,Weitao Yang,Shuzhan Shen,Chao Wu,Long Wen,Qian Cheng,Bingbo Zhang,Xiuli Wang

Elevated hydrogen peroxide (H2O2) in biological tissues is generally recognized to be relevant to the carcinogenesis process that regulates the proliferative activity of cancer cells and the transformation of malignant features. Inspired by this observation, it can be hypothesized that imaging H2O2 in the tumor microenvironment (TME) could help diagnose tumor types and malignancy, and even guide precise therapy. Thus, in this study, a noninvasive photomedicine strategy is demonstrated that leverages the different levels of H2O2 in the TME, and two representative skin cancers, malignant melanoma (MM, clinically higher incidence of metastasis and recurrence) and cutaneous squamous cell carcinoma (cSCC, relatively less dangerous), are differentially diagnosed. The working probe used here is one we previously developed, namely, intelligent H2O2 responsive ABTS-loaded HRP@Gd nanoprobes (iHRANPs). In this study, iHRANPs have advantages over ratiometric imaging due to their bimodal imaging elements, in which the inherent magnetic resonance imaging (MR) mode can be used as the internal imaging reference and the H2O2 responsive photoacoustic (PA) imaging modality can be used for differential diagnosis. Results showed that after intravenous injection of iHRANPs, the tumor signals on both MM and cSCC are obviously enhanced without significant difference under the MR modality. However, under the PA modality, MM and cSCC can be easily distinguished with obvious variations in signal enhancement. Particularly, guided by PA imaging, photothermal therapy (PTT) can be precisely applied on MM, and a strong antitumor effect was achieved owing to the excessive H2O2 in the TME of MM. Furthermore, exogenous H2O2 was injected into cSCC to remedy H2O2 deficiency in the TME of cSCC, and an evident therapeutic efficacy on cSCC can also be realized. This study demonstrated that MM can be differentially diagnosed from cSCC by noninvasive imaging of H2O2 in the TME with iHRANPs; meanwhile, it further enabled imaging-guided precision PTT ablation, even for those unsatisfactory tumor types (cSCC) through exogenously delivering H2O2.

研究领域: 肿瘤学 · 光医学 · 生物医学工程 · 分子影像 · 诊疗一体化
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BIOMATERIALS · 2021 · IF 12.479

CO/chemosensitization/antiangiogenesis synergistic therapy with H2O2-responsive diselenide-containing polymer

Jichun Yang,Shuojiong Pan,Shiqian Gao,Tianyu Li,Huaping Xu

Carbon monoxide (CO) therapy and antiangiogenesis therapy (AAT) are regarded as promising approaches for cancer treatment. However, the poor tumor targeting ability and inevitable side effects prevent their clinical application. In this study, we developed H 2 O 2 -responsive diselenide-containing micelles that combined CO therapy with chemosensitization therapy and AAT in a single system. Under the interaction of intratumoral H 2 O 2 , CO and gemcitabine (GEM) were released in situ from the micelles to reduce side effects, and CO significantly sensitized the chemotherapeutic effect of GEM by elevating the level of reactive oxygen species (ROS) in human gastric cancer AGS cells. Furthermore, diselenide bonds in the micelles were oxidized to seleninic acid in organic form, which suppressed the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to realize AAT. This study provides an integrated solution to combine CO therapy with chemosensitization therapy and AAT together with good biocompatibility .

研究领域: 癌症治疗 · 药学 · 材料科学 · 生物医学工程
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