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一种具有金纳米晶的同型膜伪装仿生纳米平台,用于协同光热/饥饿/免疫治疗。

A Homotypic Membrane-Camouflaged Biomimetic Nanoplatform with Gold Nanocrystals for Synergistic Photothermal/Starvation/Immunotherapy.

机构信息

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.

Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China.

出版信息

ACS Appl Mater Interfaces. 2021 May 26;13(20):23469-23480. doi: 10.1021/acsami.1c04305. Epub 2021 May 17.

Abstract

Although photothermal therapy (PTT) has great potential for tumor inhibition, this single mode of action frequently encounters recurrence and metastasis, highlighting the urgent need for developing combination therapy. Inspired by established evidence that PTT could induce efficient immunogenic cell death (ICD), we here developed a versatile biomimetic nanoplatform (denoted as AuDRM) for the synergism of photothermal/starvation/immunotherapy against cancer. Specifically, dendritic mesoporous silica nanoparticles (NPs) were successfully constructed followed by the synthesis of Au NPs in the mesopores. Afterward, a hybrid membrane was coated to facilitate the loading of R837. Upon efficient accumulation in the tumor tissue by homotypic targeting, the pH-sensitive membrane could be jettisoned to ensure the exposure of Au NPs for starvation therapy and the effective release of the immunostimulator R837 for enhancement of immunotherapy. Except for the PTT-mediated tumor ablation, the induction of ICD coupled with the release of tumor antigens could work synergistically with the immunostimulator R837 for inhibiting the primary tumor as well as the metastasis and induce a long-term immune memory effect for tumor inhibition a vaccine-like function. Thus, this study paves the way for high-performance tumor ablation by the synergism of photothermal/starvation/immunotherapy.

摘要

尽管光热疗法(PTT)在肿瘤抑制方面具有巨大的潜力,但这种单一作用模式经常会遇到复发和转移的问题,这凸显了开发联合治疗的迫切需要。受 PTT 可诱导有效免疫原性细胞死亡(ICD)这一既定证据的启发,我们在此开发了一种多功能仿生纳米平台(表示为 AuDRM),用于协同光热/饥饿/免疫疗法治疗癌症。具体来说,成功构建了树枝状介孔硅纳米颗粒(NPs),然后在介孔中合成了 Au NPs。之后,涂覆了混合膜以方便负载 R837。通过同种型靶向在肿瘤组织中有效积累后,pH 敏感膜可以被丢弃,以确保 Au NPs 暴露于饥饿疗法,并有效释放免疫刺激剂 R837,以增强免疫疗法。除了 PTT 介导的肿瘤消融外,ICD 的诱导与免疫刺激剂 R837 的释放相结合,可协同抑制原发肿瘤以及转移,并诱导长期的免疫记忆效应,从而实现肿瘤抑制的类似疫苗的功能。因此,这项研究为光热/饥饿/免疫治疗的协同作用实现高性能肿瘤消融铺平了道路。

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