Small
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2025
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IF 12.1
Jiaojiao Tao,Yu Dong,Bingjie Wang,Teng Wang,Aijia Zhang,Shuang Li,Rui Chen,Yanguo Su,Tianze Jiang,Xia Zhao
Immunotherapy is a promising new approach for tumor treatment. However, its clinical application is hindered by insufficient immunogenicity, hypoxia, and immunosuppressive tumor microenvironment (TME). Here, oxygen pump microneedles (OPMNs) loaded with zinc-doped copper sulfide nanoflowers (ZCS NFs) and PD-L1 small interfering RNA (siPD-L1) (OPMNs-ZCS@siPD-L1) are developed for boosting tumor immunotherapy. OPMN-ZCS@siPD-L1 enhances tumor immunogenicity through ZCS NFs by inducing cuproptosis, reverses TME through siPD-L1, and promotes drug penetration, and ameliorates hypoxia through oxygen bubbles. More importantly, cuproptosis-induced mitochondrial DNA (mtDNA) together with Zn 2+ co-activate the STING pathway, triggering a robust immune response. OPMN-ZCS@siPD-L1 increases the sensitivity to cuproptosis and induces immunogenic cell death (ICD) in vivo and in vitro, which significantly inhibits tumor progression and metastasis. The novel strategy of “increasing the throttle” (cuproptopsis-mediated STING activation & ICD effect) combined with “releasing the brake” (PD-L1 inhibition & hypoxia improvement) provides a new approach for enhancing percutaneous tumor immunotherapy.
研究领域:
肿瘤学
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免疫学
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纳米医学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2020
·
IF 3.644
Sun Tao,Zhang Yingying,Zhang Chaonan,Wang Hanjie,Pan Huizhuo,Liu Jing,Li Zhixiang,Chen Lei,Chang Jin,Zhang Weiwen
Hypoxia not only alters tumor microenvironment but leads to the tumor progression and metastasis as well as drug resistance. As a promising strategy, photodynamic therapy (PDT) can inhibit tumor by catalyzing O2 to cytotoxic reactive oxygen species. However, its effects were limited by hypoxia and in turn deteriorate hypoxia due to O2 consumption. Hereon, aiming to alleviate hypoxia and promote PDT, a bio-oxygen pump was created based on cyanobacteria, which are the only prokaryotic organisms performing oxygenic photosynthesis. Detailly, controlled-release PDT via loading indocyanine green into mesoporous silica nanoparticles was established. Then bio-oxygen pump based on a fast-growing cyanobacterium Synechococcus elongatus UTEX 2973 was tested and further packaged together with PDT to create an injectable hydrogel. The packaged hydrogel showed stable oxygen production and synergetic therapy effect especially toward hypoxia 4T1 cells in vitro. More importantly, strong in vivo therapeutic effect reaching almost 100% inhibition on tumor tissues was realized using PDT equipped with oxygen pump, with only negligible in vivo side effect on healthy mice from S. elongatus UTEX 2973. The new photo-oxygen-dynamic therapy presented here provided a promising strategy against hypoxia-resistant tumor and may worth further modifications for therapeutic application.
研究领域:
生物医学工程
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肿瘤学
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Xingchen Li,Ming Hao,Annan Liu,Lei Li,Maja D. Nešić,Bai Yang,Weiwei Liu,Quan Lin
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck region, and its treatment is limited by hypoxia and inadequate oxygen supply. Continuous oxygen delivery combined with photodynamic therapy (PDT) is the key to addressing this issue. Here, a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform was designed to serve as an "oxygen pump" to alleviate tumor hypoxia for synergistic photodynamic/photothermal therapy (PTT). In this design, the photosensitizer chlorin e6 (Ce6) is covalently linked to the Au@Pt nanozyme for PDT treatment. The Au@Pt nanozyme exhibits catalase-like activity, continuously decomposing H 2 O 2 in the tumor microenvironment to enhance O 2 levels, thereby achieving efficient PDT. Furthermore, Au@Pt can perform PTT and increase oxygen levels under NIR-II light to further promote PDT. The Au@Pt nanozyme also exhibits peroxidase-like activity, generating ·OH for chemodynamic therapy (CDT). Additionally, HN-1 guides the direction of "sniping" OSCC, and its high specificity benefits Au@Pt-Ce6-HN-1 at the tumor site. Au@Pt-Ce6-HN-1 exhibits bright fluorescence (FL), strong CT signal, and photothermal imaging capabilities, laying the foundation for subsequent guided PDT/PTT. This nanoplatform, which combines advantages such as continuous oxygen production, tumor targeting, and multimodal imaging, is expected to provide valuable insights into the treatment of OSCC. Statement of Significance Accurate clinical diagnosis and treatment of OSCC are challenging. We report a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform, serving as an "oxygen pump" to guide photodynamic therapy (PDT) and photothermal therapy (PTT) for OSCC. This nanoplatform targets OSCC for preoperative CT diagnosis and offers fluorescence visualization for surgical navigation, demonstrating potential in clinical cancer detection and surgery guidance. This innovative approach addresses OSCC hypoxia and enhances treatment efficacy through continuous oxygen production, tumor targeting, and multimodal imaging, significantly improving patient outcomes in OSCC treatment.
研究领域:
癌症治疗
·
纳米技术
·
光疗
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医学成像
·
生物医学工程
✓ 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）