The complex biology of glioma compromises therapeutic efficacy and results in poor prognosis. Photodynamic therapy (PDT) has emerged as a promising modality for localized tumor ablation with limited damage to healthy brain tissues. However, low photosensitizer concentration and hypoxic microenvironment in glioma tissue hamper the practical applications of PDT. To address the challenges, biocompatible periodic mesoporous organosilica coated Prussian blue nanoparticles (PB@PMOs) are constructed to load a biosafe prodrug 5-aminolevulinic acid (5-ALA), which is pronouncedly converted to protoporphyrin IX (PpIX) in malignant cells. PB@PMO-5-ALA induces a higher accumulation of PpIX in glioma cells compared to free 5-ALA. Meanwhile, the PB@PMOs, with a mean edge length of 81 nm and good biocompatibility, effectively decompose hydrogen peroxide to oxygen in a temperature-responsive manner. Oxygen supply further contributes to the promotion of 5-ALA-PDT. Thus, the photodynamic effect of PB@PMO-5-ALA is significantly improved, imposing augmented cytotoxicity to glioma U87MG cells. Furthermore, ex vivo fluorescence imaging elucidates the tumor PpIX increases by 75% in PB@PMO-5-ALA treated mice than that in 5-ALA treated ones post 12 h injection. Magnetic resonance imaging (MRI) and iron staining strongly demonstrate the accumulation of PB@PMO-5-ALA in glioma tissues with negative contrast enhancement and blue staining deposits, respectively. The nanoparticle accumulation and high PpIX level collaboratively enhance PDT efficacy through PB@PMO-5-ALA, which efficiently suppresses tumor growth, providing a promising option with safety for local glioma ablation.

中文翻译：

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通过负载5-氨基乙酰丙酸的纳米平台，提高选择性光敏剂的积累和氧气供应，以实现针对胶质瘤的高效光动力疗法。

胶质瘤的复杂生物学损害了治疗功效并导致不良预后。光动力疗法（PDT）已经成为一种有希望的局部肿瘤消融方法，对健康的脑组织的损害有限。然而，神经胶质瘤组织中低的光敏剂浓度和低氧微环境阻碍了PDT的实际应用。为了应对挑战，构建了具有生物相容性的周期性介孔有机硅涂层的普鲁士蓝纳米颗粒（PB @ PMO），以加载生物安全的前药5-氨基乙酰丙酸（5-ALA），该药物在恶性细胞中明显转化为原卟啉IX（PpIX）。与游离的5-ALA相比，PB @ PMO-5-ALA在胶质瘤细胞中诱导更高的PpIX积累。同时，PB @ PMO的平均边缘长度为81 nm，具有良好的生物相容性，有效地将过氧化氢以温度响应方式分解为氧气。氧气供应进一步促进了5-ALA-PDT的发展。因此，PB @ PMO-5-ALA的光动力作用得到了显着改善，对神经胶质瘤U87MG细胞的细胞毒性增强。此外，离体荧光成像表明，在注射12小时后，PB @ PMO-5-ALA处理的小鼠中的肿瘤PpIX比5-ALA处理的小鼠增加了75％。磁共振成像（MRI）和铁染色强烈地证明了PB @ PMO-5-ALA在神经胶质瘤组织中的积累，分别具有负的对比度增强和蓝色染色沉积。纳米颗粒的积累和高PpIX水平通过PB @ PMO-5-ALA协同增强了PDT的功效，从而有效地抑制了肿瘤的生长，