Wei Cheng's second work, which focuses on remodeling macrophages combined with non-invasive sonodynamic therapy for the treatment of glioblastoma, has been published in ACS Nano (IF = 16). Congratulations! 

胶质母细胞瘤（GBM）是中枢神经系统中最具侵袭性的恶性肿瘤，其治疗面临多重挑战。首先，血脑屏障（BBB）作为一道天然屏障，限制了药物进入脑组织的效率，导致许多传统治疗手段难以有效作用于肿瘤部位。其次，GBM的肿瘤免疫微环境（TIME）高度抑制，富含免疫抑制细胞，尤其是肿瘤相关巨噬细胞（TAMs），其中M2型巨噬细胞占比高达30-50%，它们通过分泌促肿瘤因子加速肿瘤生长并抑制抗肿瘤免疫反应。此外，全身免疫抑制和T细胞储备不足进一步削弱了机体对GBM的免疫防御能力。现有治疗手段，如手术、放疗和化疗，平均仅能将患者生存期延长至约15个月，5年生存率低于6%，且复发率接近100%，几乎无法实现治愈。因此，开发能够克服血脑屏障、调控肿瘤微环境并激活全身免疫的综合治疗策略，成为GBM治疗领域的研究热点。

针对以上问题，团队在前期跨生物屏障纳米药物及脑部疾病靶向治疗研究基础（ACS Nano, 2025, 19, 557; Nano Research, 2025, 18, 94907338; Acta Biomaterialia 2025, 193, 392; ACS Nano 2024, 18, 28228; Nature Communications 2018, 9, 3653; Nature Nanotechnology, 2020, 15, 482）上，开发序贯靶向声动力纳米疫苗（Stars NV），该疫苗能避免循环巨噬细胞的吞噬，有效穿越血脑屏障，并序贯靶向肿瘤相关巨噬细胞（TAMs）。在超声波激发下，Stars NV以非侵入性方式消融胶质瘤，同时诱导适应性抗胶质瘤免疫反应，形成个性化的原位疫苗，并释放R848以重塑抑制性肿瘤微环境。此外，Stars NV激活全身免疫，促进胸腺中T细胞的生成、淋巴结中的成熟、血液中的循环以及向重塑后肿瘤微环境的招募。在颅内胶质瘤小鼠模型中，Stars NV将中位生存期从23天延长至超过60天，使M1/M2巨噬细胞比例提升31倍，肿瘤浸润淋巴细胞增加5.2倍，同时降低Tregs 5.5倍。它还显著增强全身免疫，使外周CD4+和CD8+T细胞分别增加2.4倍和5.4倍。Stars NV启动了一个局部与全身免疫的自我强化循环，为胶质瘤治疗提供了极具前景的策略，有望大幅改善疗效。相关研究成果以“Noninvasive Activation of Local and Systemic Immunity with a Sequential-Targeting Sonodynamic Nanovaccine to Treat Glioblastoma”为题，发表于期刊《ACS Nano》。

Abstract:

Glioblastoma (GBM) presents significant therapeutic challenges due to the blood-brain barrier (BBB), suppressive tumor immune microenvironment (TIME), and systemic immunosuppression with limited T cell reserves. We developed a sequential-targeting sonodynamic nanovaccine (Stars NV) that avoids circulating macrophage uptake, efficiently crosses BBB, and sequentially targets tumor-associated macrophages (TAMs). Under ultrasound stimulation, Stars NV noninvasively ablates GBM and induces adaptive anti-GBM immunity, functioning as a personalized in situ vaccine. Simultaneously, it releases R848 to reprogram the suppressive TIME. Additionally, Stars NV activates systemic immunity, promoting T cell generation in the thymus, maturation in lymph nodes, circulation in the bloodstream, and recruitment into the reprogrammed TIME. In an intracranial GBM mouse model, Stars NV extended median survival from 23 to over 60 days, elevated the M1/M2 TAM ratio by 31-fold and tumor-infiltrating lymphocytes by 5.2-fold, and lowered the Tregs by 5.5-fold. It also boosted systemic immunity, increasing peripheral CD4⁺ and CD8⁺ T cells by 2.4-fold and 5.4-fold, respectively. The Stars NV initiates a self-reinforcing cycle of local and systemic immunity, offering a promising strategy for GBM that holds substantial potential to enhance therapeutic outcomes.