Biomaterials Science
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2023
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IF 6.6
Xin Jin,Zelin Ou,Guowei Zhang,Rong Shi,Jumin Yang,Wenguang Liu,Gaoxing Luo,Jun Deng,Wei Wang
With an increasing proportion of drug-resistant bacteria, photothermal therapy (PTT) is a promising alternative to antibiotic treatment for infected diabetic skin ulcers. However, the inevitable thermal damage to the tissues restricts its clinical practice. Carbon monoxide (CO), as a bioactive gas molecule, can selectively inhibit bacterial growth and promote tissue regeneration, which may be coordinated with PTT for drug-resistant bacteria killing and tissue protection. Herein, a CO-mediated PTT agent (CO@mPDA) was engineered by loading manganese carbonyl groups into mesoporous polydopamine (mPDA) nanoparticles via coordination interactions between the metal center and a catechol group. Compared to the traditional PTT, the CO-mediated PTT increases the inhibition ratio of the drug-resistant bacteria both in vitro and in diabetic wound beds by selectively inhibiting the co-chaperone of the heat shock protein 90 kDa (Hsp90), and lowers the heat resistance of the bacteria rather than the mammalian tissues. Meanwhile, the tissue-protective proteins, such as Hsp90 and vimentin (Vim), are upregulated via the WNT and PI3K-Akt pathways to reduce thermal injury, especially with a laser with a high-power density. The CO-mediated PTT unified the bacterial killing with tissue protection, which offers a promising concept to improve PTT efficiency and minimize the side-effects of PTT when treating infected skin wounds.
研究领域:
生物医学工程
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纳米技术
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药学
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伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced NanoBiomed Research
·
2024
·
IF 4
Yile Zheng,Yi Wei,Yuying Yang,Xiang Wen,Cai Yang,Yating Xiao,Zhen Du,Xiangsheng Liu
Photoactivatable carbon monoxide-releasing molecules (CORMs), typically based on transition-metal carbonyl complexes, have reliance on activation by UV or visible light that restricts their biomedical applications. To address this limitation, a near-infrared (NIR)-responsive nanoplatform is presented based on upconversion nanoparticles (UCNPs) loading with manganese carbonyl complex Mn 2 (CO) 10 that concurrently releases CO and manganese ion (Mn 2+ ). With the UCNPs, the more tissue-penetrable NIR is used to locally generate UV light for photodecomposition of Mn 2 (CO) 10 into CO and manganese oxide (MnO X ), after which MnO X is reduced to Mn 2+ by the overexpressed glutathione in cancer cells. Moreover, the released Mn 2+ can serve as a magnetic resonance imaging contrast agent to monitor the NIR-controlled corelease of CO and Mn 2+ in real time. Therefore, this nanoplatform can provide a potential strategy for NIR-enabled spatiotemporally release of CO and Mn 2+ , enhancing the controlled delivery and biomedical application of CORMs.
研究领域:
生物医学工程
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纳米技术
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药学科学
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成像技术
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治疗诊断学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yang Wang,Danni Jing,Jiawen Yang,Shajun Zhu,Jian Shi,Xiru Qin,Wujie Yin,Jin Wang,Yue Ding,Tingting Chen,Bing Lu,Yong Yao
Carbon monoxide (CO) as one of the therapeutic gaseous molecules has been widely applied for treating various diseases, especially in cancer therapy. However, the in situ-triggered and efficient transport of CO to tumors are the primary obstacles that limit its clinical applicability. To address this obstacle, herein, a H 2 O 2 -triggered CO gas releasing nanoplatform has been designed by embedding manganese carbonyl (MnCO) into Zr (IV)-based metal-organic frameworks (MOFs). The porous structures of MOFs provide encapsulation capacity for glucose oxidase (GOx) loading, thereby catalyzing the endogenous glucose into gluconic acid and H 2 O 2 to accelerate CO release and energy depletion. In the meantime, the Mn 2+ produced by MnCO can react with intracellular H 2 O 2 via the Fenton reaction to form cytotoxic •OH. Therefore, the synthesized gas nanogenerator demonstrated a synergistic efficacy of CO gas therapy, reactive oxygen species (ROS)-mediated therapy, and energy starvation to prevent tumor growth. Both in vitro and in vivo studies indicated that this multifunctional nanoplatform not only successfully inhibited tumors through a synergistic effect, but also provided a new technique for the creation of starvation/gas/chemodynamic combination therapy in a single material. Statement of significance In this study, we developed a H 2 O 2 responsive CO gas nanogenerator to augment the in-situ generation of CO gas for combined modality therapy of tumors. The nanogenerator was constructed by encapsulating glucose oxidase (GOx) and manganese carbonyl (MnCO) into UiO-67-bpy, which can catalyze the conversion of intracellular glucose to H 2 O 2 for cutting off energy supply of cancer cells. Meanwhile, the cumulated H 2 O 2 can trigger the release of CO for gas therapy and generation of •OH for chemodynamic therapy (CDT) via the Fenton-like reaction, thereby resulting in apoptosis of the cancer cells. Collectively, our designed nanotherapeutic agent not only displays the synergistic therapy efficacy of starvation-enhanced CO gas therapy and CDT, but also provides an efficient strategy for developing the intelligent nanocarrier for CO gas delivery and release.
研究领域:
癌症治疗
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材料科学
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生物医学工程
·
化学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Geng Yang,Ting Song,Hanxi Zhang,Mengyue Li,Xiaodan Wei,Wanyi Zhou,Chunhui Wu,Yiyao Liu,Hong Yang
Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H 2 O 2 -rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn 2+ enables T 1 -weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction.
研究领域:
癌症治疗
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材料科学
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生物医学工程
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Jianrong Wu,Zheying Meng,Agata A. Exner,Xiaojun Cai,Xue Xie,Bing Hu,Yu Chen,Yuanyi Zheng
Gas therapy as an emerging therapeutic modality for cancer treatment is still facing critical challenges such as precise delivery and controllable release of therapeutic gas. Herein, we report a “tumor-microenvironment remodeling” strategy for in situ sustained release of CO gas and magnetic resonance imaging (MRI)-monitored targeted/synergistic cancer gas/starvation nanotherapy by engineering cascade biodegradable nanocatalyst . The nanocatalyst integrates the enzyme catalyst glucose oxidase (GOD) and H 2 O 2 -sensitive molecule manganese carbonyl (MnCO) entrapped biodegradable hollow mesoporous organosilica nanoparticles (HMONs). Especially, GOD is initially exploited as a gatekeeper, followed by surface engineering with arginine-glycine-aspartic acid (RGD) for specifically targeting α v β 3 integrin-overexpressed cancer cells. The GOD is dissociated under reduced pH to release the loaded MnCO, and sequentially produce gluconic acid and H 2 O 2 to remodel the TME for facilitating the in situ generation of CO/Mn 2+ . As systematically demonstrated both at cellular level and in an animal tumor xenograft model, the engineered nanocatalyst achieves superior theranostics performance via combinatorial CO gas and starving-like nanotherapy. This work provides an effective strategy for augmenting CO-mediated antitumor efficacy by remodeling the tumor microenvironment .
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）