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Sequence-Responsive Multifunctional Supramolecular Nanomicelles Act on the Regression of TNBC and Its Lung Metastasis via Synergic Pyroptosis-Mediated Immune Activation
Small ( IF 13.0 ) Pub Date : 2023-08-27 , DOI: 10.1002/smll.202305101
Xing Wang 1 , Yuanhang Li 1 , Kamran Hasrat 1 , Li Yang 1 , Zhengjian Qi 1
Small ( IF 13.0 ) Pub Date : 2023-08-27 , DOI: 10.1002/smll.202305101
Xing Wang 1 , Yuanhang Li 1 , Kamran Hasrat 1 , Li Yang 1 , Zhengjian Qi 1
Affiliation
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Design of effective nanodrugs to modulate the immunosuppression of tumor microenvironment is a desirable approach to boost the clinical tumor-therapeutic effect. Supramolecular nanomicelles PolyMN-TO-8, which are constructed by self-assembling supramolecular host MTX-MPEG2000, guest NPX-2S, and TO-8 through hydrophobic forces, have excellent stability and responsiveness to carboxylesterase and glutathione in turn. In vivo studies validate that PolyMN-TO-8 enable to trigger pyroptosis-mediated immunogenic cell death under laser, avoiding the occurrence of immune dysregulation simultaneously. This therapeutic mode strengthens dendritic cells’ maturation and accelerates the infiltration of CD8+ T cells into tumors through moderate activation of pro-inflammatory factors with elimination of immune-escape, ultimately making the tumor inhibition rate as high as 87.44% via synergistic functions of photodynamic therapy, photothermal therapy, chemotherapy, etc. The loss of immune-escape quickens the infiltration of CD8+ T cells into lungs, and further eschews the generation of tumor nodules in it. Chemotherapy, the release of interferon-γ, and immune memory effect also strengthen the defense against metastasis. The generation of O2 catalyzed by PolyMN-TO-8 under laser is indispensable for tumor metastasis inhibition undoubtedly.
中文翻译：
序列响应性多功能超分子纳米胶束通过协同焦亡介导的免疫激活作用于 TNBC 的消退及其肺转移
设计有效的纳米药物来调节肿瘤微环境的免疫抑制是提高临床肿瘤治疗效果的理想方法。超分子纳米胶束 PolyMN-TO-8 由超分子宿主 MTX-MPEG2000、客体 NPX-2S 和 TO-8 通过疏水力自组装构建，具有优异的稳定性和对羧酸酯酶和谷胱甘肽的响应性。体内研究证实 PolyMN-TO-8 能够在激光下触发焦亡介导的免疫原性细胞死亡，同时避免免疫失调的发生。这种治疗模式通过适度激活促炎因子，消除免疫逃逸，加强树突状细胞的成熟，加速 CD8+ T 细胞浸润肿瘤，最终通过光动力疗法、光热疗法、化疗等的协同作用，使肿瘤抑制率高达 87.44%。免疫逃逸的丧失加速了 CD8+ T 细胞浸润到肺部，并进一步避免了其中肿瘤结节的产生。化疗、干扰素γ释放和免疫记忆效应也增强了对转移的防御能力。在激光下 PolyMN-TO-8 催化的 O2 的产生无疑对于肿瘤转移抑制是必不可少的。
更新日期：2023-08-27
中文翻译：
序列响应性多功能超分子纳米胶束通过协同焦亡介导的免疫激活作用于 TNBC 的消退及其肺转移
设计有效的纳米药物来调节肿瘤微环境的免疫抑制是提高临床肿瘤治疗效果的理想方法。超分子纳米胶束 PolyMN-TO-8 由超分子宿主 MTX-MPEG2000、客体 NPX-2S 和 TO-8 通过疏水力自组装构建，具有优异的稳定性和对羧酸酯酶和谷胱甘肽的响应性。体内研究证实 PolyMN-TO-8 能够在激光下触发焦亡介导的免疫原性细胞死亡，同时避免免疫失调的发生。这种治疗模式通过适度激活促炎因子，消除免疫逃逸，加强树突状细胞的成熟，加速 CD8+ T 细胞浸润肿瘤，最终通过光动力疗法、光热疗法、化疗等的协同作用，使肿瘤抑制率高达 87.44%。免疫逃逸的丧失加速了 CD8+ T 细胞浸润到肺部，并进一步避免了其中肿瘤结节的产生。化疗、干扰素γ释放和免疫记忆效应也增强了对转移的防御能力。在激光下 PolyMN-TO-8 催化的 O2 的产生无疑对于肿瘤转移抑制是必不可少的。
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