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ZnO-based multifunctional nanocomposites to inhibit progression and metastasis of melanoma by eliciting antitumor immunity via immunogenic cell death

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单位: [1]Huazhong Univ Sci & Technol HUST, Union Hosp, Tongji Med Coll, Dept Dermatol, Wuhan 430022, Peoples R China [2]HUST, Sch Chem & Chem Engn, Minist Educ, Key Lab Mat Chem Energy Convers & Storage, Wuhan 430074, Peoples R China [3]HUST, Tongji Med Coll, Union Hosp, Dept Hematol, Wuhan 430022, Peoples R China [4]HUST, Tongji Med Coll, Cent Hosp Wuhan, Dept Dermatol, Wuhan 430022, Peoples R China [5]HUST, Tongji Med Coll, Union Hosp, Clin Lab, Wuhan 430022, Peoples R China [6]Huazhong Univ Sci & Technol HUST, Tongji Hosp, Tongji Med Coll, Dept Dermatol, Wuhan 430022, Peoples R China [7]Rutgers RWJMS, Dept Dermatol, Somerset, NJ USA [8]Cent South Univ, XiangYa Hosp, Dept Dermatol, Changsha 410008, Peoples R China [9]HUST, Dept Immunol, Tongji Med Coll, Wuhan 430022, Peoples R China
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关键词: ZnO Nanoparticles Immunogenic Cell Death Thermo-chemotherapy Mesoporous Silica Nanoparticles Melanoma

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Rationale: The development of a highly effective and tumor-specific therapeutic strategy, which can act against the primary tumor and also condition the host immune system to eliminate distant tumors, remains a clinical challenge. Methods: Herein, we demonstrate a facile yet versatile ZnO-capping and Doxorubicin (DOX)-loaded multifunctional nanocomposite (AuNP(C)mSiO(2)@DOX-ZnO) that integrates photothermal properties of gold nanoparticles (NPs), pH-responsive properties and preferential selectivity to tumor cells of ZnO QDs and chemotherapeutic agent into a single NP. The photothermal performance, pH-triggered release and preferential phagocytic ability were assessed. The induced anti-tumor immunity was determined by analyzing immune cell profile in tumor in vivo and molecular mechanism were identified by detecting expression of immunogenic cell death (ICD) markers in vitro. Moreover, mice models of unilateral and bilateral subcutaneous melanoma and lung metastasis were established to evaluate the antitumor effects. Results: As an efficient drug carrier, ZnO-capped NPs guarantee a high DOX payload and an in vitro, efficient release of at pH 5.0. In murine melanoma models, the nanocomposite can significantly inhibit tumor growth for a short period upon low-power laser irradiation. Importantly, ZnO NPs not only demonstrate preferential selectivity for melanoma cells but can also induce ICD. Meanwhile, AuNP@mSiO(2)-based photothermal therapy (PTT) and DOX are directly cytotoxic towards cancer cells and demonstrate an elevated ICD effect. The induced ICD promotes maturation of dendritic cells, further stimulating the infiltration of effector T cells into tumor sites, preventing tumor growth and distant lung metastases. Conclusions: This study highlights the novel mechanism of ZnO-triggered anti-tumor immunity via inducing ICD. Additionally, we shed light on the multifunctionality of nanocomposites in delivering localized skin tumor therapy as well as inhibiting metastatic growth, which holds great promise in clinical applications.

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出版当年[2019]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
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出版当年[2018]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
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Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者单位: [1]Huazhong Univ Sci & Technol HUST, Union Hosp, Tongji Med Coll, Dept Dermatol, Wuhan 430022, Peoples R China
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