Research Center of Cancer Diagnosis and Therapy, Department of Oncology, The First Affiliated Hospital, and Department of Chemistry, Jinan University, Guangzhou, 510632, China.
Department of Respiratory Disease, The State Key Laboratory of Respiratory Disease, China Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Adv Healthc Mater. 2021 Jun;10(12):e2100149. doi: 10.1002/adhm.202100149. Epub 2021 Apr 18.
Malignant pleural effusion (MPE) remains a treatment bottleneck in advanced lung cancer, due to its complicated microenvironments and "cold" immunity. Therefore, the search for therapeutic drugs to transform MPE to functionally "hot" one could advance the development of effective immunotherapeutic strategy. Herein, translational selenium nanoparticles coated with immune-modulating macromolecule lentinan (SeNPs@LNT) are designed to restore the dysfunctional immune cells in patient-derived MPE microenvironment. Internalization of the SeNPs@LNT can effectively reduce the immunosuppressive status by enhancing the proliferation of CD4 T cells and natural killer cells, and remodeling the tumor associated macrophages into tumoricidal M1 phenotype in MPE derived from patients presenting low Se levels in blood and pleural effusion. Th1, cytotoxic T cell, γδ T, and B cell functions are upregulated, and Th2, Th17, and Treg cells activity is downregulated. Furthermore, SeNPs@LNT can be gradually metabolized into SeCys2 to promote the production of metabolites associated with tumor growth inhibition and immune response activation in MPE microenvironment. In contrast, lung cancer markers and vitamin B6 metabolism are decreased. The translational SeNP-based nanotherapeutic strategy restores functional "cold" MPE to "hot" MPE to activate the immune responses of various immune cells in MPE of lung cancer patients.
恶性胸腔积液（MPE）仍然是晚期肺癌治疗的瓶颈，这是由于其复杂的微环境和“冷”免疫。因此，寻找治疗药物将 MPE 转化为功能上的“热”状态，可以推进有效的免疫治疗策略的发展。在此，设计了一种用免疫调节大分子香菇多糖（LNT）修饰的翻译硒纳米颗粒（SeNPs@LNT），以恢复患者来源的 MPE 微环境中功能失调的免疫细胞。SeNPs@LNT 的内化可以通过增强 CD4 T 细胞和自然杀伤细胞的增殖，将肿瘤相关巨噬细胞重塑为杀伤性 M1 表型，从而有效地减轻免疫抑制状态，而这些表型在血液和胸腔积液中硒水平较低的患者中产生。Th1、细胞毒性 T 细胞、γδ T 和 B 细胞功能上调，而 Th2、Th17 和 Treg 细胞活性下调。此外，SeNPs@LNT 可以逐渐代谢为 SeCys2，以促进与肿瘤生长抑制和免疫反应激活相关的代谢产物在 MPE 微环境中的产生。相比之下，肺癌标志物和维生素 B6 代谢减少。基于翻译硒纳米颗粒的纳米治疗策略将功能上的“冷”MPE 恢复为“热”MPE，以激活肺癌患者 MPE 中各种免疫细胞的免疫反应。
