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白蛋白纳米粒载吲哚菁绿和阿霉素的光热/化学协同治疗导致黑色素瘤细胞免疫原性细胞死亡。

Dual Photothermal/Chemotherapy of Melanoma Cells with Albumin Nanoparticles Carrying Indocyanine Green and Doxorubicin Leads to Immunogenic Cell Death.

机构信息

Materials Science, Engineering and Commercialization Program, Texas State University, 601 University Drive, San Marcos, TX, 78666, USA.

Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton Street, Austin, TX, 78712, USA.

出版信息

Macromol Biosci. 2022 Feb;22(2):e2100353. doi: 10.1002/mabi.202100353. Epub 2021 Nov 19.

Abstract

Recent focus on cancer immunotherapies has led to significant interest in the development of therapeutic strategies that can lead to immunogenic cell death (ICD), which can cause activation of an immune response against tumor cells and improve immunotherapy outcomes by enhancing the immunogenicity of the tumor microenvironment. In this work, a nanomedicine-mediated combination therapy is used to deliver the ICD inducers doxorubicin (Dox), a chemotherapeutic agent, and indocyanine green (ICG), a photothermal agent. These agents are loaded into nanoparticles (NPs) of bovine serum albumin (BSA) that are prepared through a desolvation process. The formulation of BSA NPs is optimized to achieve NPs of 102.6  nm in size and loadings of 8.55 % and 5.69 % (w/w) for ICG and Dox, respectively. The controlled release of these agents from the BSA NPs is confirmed. Upon laser irradiation for 2.5 min, NPs at a dose of 62.5 μg mL are able to increase the temperature of the cells by 7 °C and thereby inhibit the growth of B16F10 melanoma cells in vitro. Surface presentation of heat shock proteins and calreticulin from the cells after treatment confirmed the ability of the Dox/ICG loaded BSA NPs to induce ICD in the melanoma cells.

摘要

最近对癌症免疫疗法的关注导致人们对开发能够导致免疫原性细胞死亡(ICD)的治疗策略产生了浓厚的兴趣,ICD 可以激活针对肿瘤细胞的免疫反应,并通过增强肿瘤微环境的免疫原性来改善免疫疗法的效果。在这项工作中,采用一种纳米医学介导的联合疗法来递送电化疗药物阿霉素(Dox)和光热试剂吲哚菁绿(ICG)这两种 ICD 诱导剂。这些药物被负载到牛血清白蛋白(BSA)纳米粒子(NPs)中,通过去溶剂化过程制备。优化了 BSA NPs 的配方,使其达到 102.6nm 的粒径,ICG 和 Dox 的载药量分别为 8.55%(w/w)和 5.69%(w/w)。从 BSA NPs 中释放这些药物得到了确认。在激光照射 2.5 分钟后,剂量为 62.5μg mL 的 NPs 能够将细胞温度升高 7°C,从而抑制体外 B16F10 黑色素瘤细胞的生长。处理后细胞表面展示热休克蛋白和钙网蛋白,证实了负载 Dox/ICG 的 BSA NPs 能够诱导黑色素瘤细胞发生 ICD。

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