将癌症相关成纤维细胞失活与免疫化疗相结合的生物反应性纳米复合物,用于重建免疫排斥肿瘤。

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-03-13 DOI:10.1016/j.nano.2024.102743
Lisha Liu PhD , Beiyuan Zhang MSc , Xianggui Wu MSc , Gang Cheng MSc , Xiaopeng Han PhD , Xiaofei Xin PhD , Chao Qin PhD , Lei Yang PhD , Meirong Huo PhD , Lifang Yin PhD
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引用次数: 0

摘要

癌症相关成纤维细胞(CAFs)在创造免疫抑制环境和重塑肿瘤内细胞外基质方面发挥着至关重要的作用,从而导致化疗耐药和免疫细胞浸润受限。为应对这些挑战,将 CAFs 失活纳入免疫化疗可能是逆转免疫排斥性肿瘤的一种有前景的方法。我们开发了一种肿瘤靶向纳米药物--谷胱甘肽响应性纳米复合物(GNC)。GNC将CAF抑制剂达沙替尼和化疗药物紫杉醇共同载入,使CAF失活,增强免疫化疗的效果。由于透明质酸的修饰作用,GNC优先积聚在肿瘤外围,并响应性地释放载体,减轻了肿瘤基质的负担,克服了化疗耐药性。此外,GNC治疗还具有显著的免疫刺激功效,包括CD8+ T细胞扩增和PD-L1下调,有利于免疫检查点阻断治疗。总之,利用 GNC 纳米平台将 CAF 失活与免疫化疗相结合,有望重建免疫排斥肿瘤。
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Bioresponsive nanocomplex integrating cancer-associated fibroblast deactivation and immunogenic chemotherapy for rebuilding immune-excluded tumors

Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.

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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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