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Targeted Reprogramming of Vitamin B3 Metabolism as a Nanotherapeutic Strategy towards Chemoresistant Cancers
Advanced Materials ( IF 27.4 ) Pub Date : 2023-06-01 , DOI: 10.1002/adma.202301257 Daoxia Guo 1 , Xiaoyuan Ji 1 , Hui Xie 2 , Jia Ma 1 , Chunchen Xu 1 , Yanfeng Zhou 1 , Nan Chen 2 , Hui Wang 1 , Chunhai Fan 3 , Haiyun Song 1
Advanced Materials ( IF 27.4 ) Pub Date : 2023-06-01 , DOI: 10.1002/adma.202301257 Daoxia Guo 1 , Xiaoyuan Ji 1 , Hui Xie 2 , Jia Ma 1 , Chunchen Xu 1 , Yanfeng Zhou 1 , Nan Chen 2 , Hui Wang 1 , Chunhai Fan 3 , Haiyun Song 1
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Cancer-associated fibroblasts (CAFs) promote cancer stem cell (CSC)-mediated chemoresistance and immunosuppressive tumor microenvironment. However, direct depletion of CAFs may increase cancer invasiveness and metastasis. As a generalized strategy against chemoresistant cancers, Gemini-like homotypic targeting nanoparticles (NPs) are designed for two-pronged CAF transformation and cancer cell elimination. The CAF-targeted NPs couple vitamin B3 metabolic reprogramming to epigenetic modulation of secreted pro-stemness and immunosuppressive factors, thereby diminishing CSC and suppressive immune cell populations to enhance cancer cell drug susceptibility and cytotoxic T cell infiltration. In mouse models of breast, liver, pancreatic and colorectal cancers that are resistant to their respective first-line chemotherapeutics, a single dose of hydrogel co-delivering the Gemini-like NPs can rehabilitate chemosensitivity, induce immune activation, and achieve tumor regression. Moreover, it stimulates robust T cell memory for long-term protection against tumor rechallenge. This study thus represents an innovative approach with broad applicability for overcoming cancer chemoresistance.
中文翻译：
维生素 B3 代谢的靶向重编程作为化疗耐药癌症的纳米治疗策略
癌症相关成纤维细胞（CAF）促进癌症干细胞（CSC）介导的化疗耐药和免疫抑制肿瘤微环境。然而，直接消耗 CAF 可能会增加癌症的侵袭和转移。作为对抗化疗耐药癌症的通用策略，Gemini 样同型靶向纳米颗粒 (NP) 旨在双管齐下地实现 CAF 转化和癌细胞消除。靶向 CAF 的 NP 将维生素 B 3代谢重编程与分泌的前干细胞和免疫抑制因子的表观遗传调节结合起来，从而减少 CSC 和抑制性免疫细胞群，从而增强癌细胞药物敏感性和细胞毒性 T 细胞浸润。在对各自的一线化疗药物耐药的乳腺癌、肝癌、胰腺癌和结直肠癌小鼠模型中，单剂量的水凝胶共同递送 Gemini 样 NP 可以恢复化疗敏感性，诱导免疫激活并实现肿瘤消退。此外，它还能刺激强大的 T 细胞记忆，从而长期防止肿瘤再次攻击。因此，这项研究代表了一种具有广泛适用性的克服癌症化疗耐药性的创新方法。
更新日期：2023-06-01
中文翻译：
维生素 B3 代谢的靶向重编程作为化疗耐药癌症的纳米治疗策略
癌症相关成纤维细胞（CAF）促进癌症干细胞（CSC）介导的化疗耐药和免疫抑制肿瘤微环境。然而，直接消耗 CAF 可能会增加癌症的侵袭和转移。作为对抗化疗耐药癌症的通用策略，Gemini 样同型靶向纳米颗粒 (NP) 旨在双管齐下地实现 CAF 转化和癌细胞消除。靶向 CAF 的 NP 将维生素 B 3代谢重编程与分泌的前干细胞和免疫抑制因子的表观遗传调节结合起来，从而减少 CSC 和抑制性免疫细胞群，从而增强癌细胞药物敏感性和细胞毒性 T 细胞浸润。在对各自的一线化疗药物耐药的乳腺癌、肝癌、胰腺癌和结直肠癌小鼠模型中，单剂量的水凝胶共同递送 Gemini 样 NP 可以恢复化疗敏感性，诱导免疫激活并实现肿瘤消退。此外，它还能刺激强大的 T 细胞记忆，从而长期防止肿瘤再次攻击。因此，这项研究代表了一种具有广泛适用性的克服癌症化疗耐药性的创新方法。
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