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./nMethods: Herein, we demonstrate a facile yet versatile ZnO-capping and Doxorubicin (DOX)-loaded multifunctional nanocomposite (AuNP@mSiO₂@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./nResults: 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@mSiO₂-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./nConclusions: 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.

中文翻译：

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基于ZnO的多功能纳米复合材料，可通过免疫原性细胞死亡引发抗肿瘤免疫，从而抑制黑素瘤的进展和转移

理由：开发一种高效且针对肿瘤的治疗策略，可以对原发性肿瘤起作用，并调节宿主免疫系统以消除远处的肿瘤，仍然是一项临床挑战。/n方法：本文证明了一种简便易行的方法多功能的ZnO封端和阿霉素（DOX）负载的多功能纳米复合材料（AuNP @ mSiO ₂ @ DOX-ZnO），具有金纳米颗粒（NPs）的光热特性，pH响应特性以及对ZnO QDs和化学治疗剂对肿瘤细胞的优先选择性。成一个NP。评估了光热性能，pH触发释放和优先吞噬能力。通过分析肿瘤中的免疫细胞谱来确定诱导的抗肿瘤免疫力在体内和分子机理进行通过检测的免疫原性细胞死亡（ICD）标志物的表达鉴定的体外。此外，建立了单侧和双侧皮下黑色素瘤和肺转移的小鼠模型以评估其抗肿瘤作用。/n结果：作为一种有效的药物载体，ZnO封端的NP保证了较高的DOX负载量和在pH下的体外有效释放5.0。在鼠类黑色素瘤模型中，在低功率激光照射下，纳米复合材料可在短期内显着抑制肿瘤生长。重要的是，ZnO NPs不仅表现出对黑色素瘤细胞的优先选择性，而且还可以诱导ICD。同时，AuNP @ mSiO ₂的光热疗法（PTT）和DOX对癌细胞具有直接的细胞毒性，并表现出较高的ICD效应。诱导的ICD促进树突状细胞的成熟，进一步刺激效应T细胞向肿瘤部位的浸润，防止肿瘤的生长和远处的肺转移。/n结论：这项研究强调了通过诱导ICD ZnO触发的抗肿瘤免疫的新机制。 。此外，我们阐明了纳米复合材料在提供局部皮肤肿瘤治疗以及抑制转移性生长方面的多功能性，这在临床应用中具有广阔的前景。