Sun Jian, Wang Deqiang, Wei Yiying, Wang Danyang, Ji Zhengkun, Sun Wanru, Wang Xin, Wang Pingyu, Basmadji Nicola Paccione, Larrarte Eider, Pedraz José Luis, Ramalingam Murugan, Xie Shuyang, Wang Ranran
Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai 264003, People's Republic of China.
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
Nanoscale. 2025 Feb 6;17(6):3288-3305. doi: 10.1039/d4nr04454a.
As a common malignancy symptom, cancer pain significantly affects patients' quality of life. Approximately 60%-90% of patients with advanced cancer experience debilitating pain. Therefore, a comprehensive treatment system that combines cancer pain suppression and tumor treatment could provide significant benefits for these patients. Here, we designed a manganese oxide (MnO)/Bovine serum albumin (BSA)/polydopamine (PDA) composite nanoplatform internally loaded with capsaicin for cancer pain suppression and immunotherapy. MBD&C nanoparticles (NPs) can ablate tumor-innervated sensory nerve fibers Transient receptor potential vanilloid 1 (TRPV1) channels, thereby reducing the pain caused by various inflammatory mediators. The ablation of TRPV1 nerve terminals can also decrease the secretion of calcitonin gene-related peptide (CGRP) and substance P (SP) in sensory nerve fibers, thus reducing the tumor pain and inhibit tumor progression. MBD&C can promote calcium influx by activating overexpressed TRPV1 channels on the tumor membrane surface, thereby achieving cancer immunotherapy induced by endogenous Ca overloading. In addition, MnO NPs can alleviate tumor hypoxia and mitigate the immunosuppressive tumor microenvironment (TME). Ultimately, this treatment system with dual capabilities of inhibiting tumor growth and relieving cancer pain makes comfortable tumor therapy feasible and paves the way for the development of patient-centered approaches to cancer treatment in the future.
作为一种常见的恶性肿瘤症状，癌痛严重影响患者的生活质量。约60%-90%的晚期癌症患者经历使人衰弱的疼痛。因此，一种将癌痛抑制与肿瘤治疗相结合的综合治疗体系可为这些患者带来显著益处。在此，我们设计了一种内部负载辣椒素的氧化锰（MnO）/牛血清白蛋白（BSA）/聚多巴胺（PDA）复合纳米平台，用于癌痛抑制和免疫治疗。MBD&C纳米颗粒（NPs）可消融肿瘤支配的感觉神经纤维上的瞬时受体电位香草酸亚型1（TRPV1）通道，从而减轻由各种炎症介质引起的疼痛。TRPV1神经末梢的消融还可减少感觉神经纤维中降钙素基因相关肽（CGRP）和P物质（SP）的分泌，从而减轻肿瘤疼痛并抑制肿瘤进展。MBD&C可通过激活肿瘤膜表面过表达的TRPV1通道促进钙内流，从而实现内源性钙过载诱导的癌症免疫治疗。此外，MnO NPs可缓解肿瘤缺氧并减轻免疫抑制性肿瘤微环境（TME）。最终，这种具有抑制肿瘤生长和缓解癌痛双重能力的治疗体系使舒适的肿瘤治疗成为可能，并为未来以患者为中心的癌症治疗方法的发展铺平了道路。
