Introduction: Traditional antitumor chemotherapy faces great challenges, such as multi-drug resistance (MDR) and poor penetration into tumor tissues. The newly emerging nitric oxide (NO)-based gas therapy has been recognized to reduce MDR and has improved permeation into tumor tissue.
Methods: In this study, NO-generating prodrug sodium nitroprusside (SNP) was doped to hollow mesoporous Prussian blue (PB) nanoparticles to fabricate NO-generating nanoparticles (NO-PB), which was further loaded with doxorubicin (DOX).
Results: DOX loaded NO-PB (DOX-NO-PB) was released quicker at pH 6 compared with neutral pH, suggesting NO-PB may facilitate the release of loaded drug in acidic tumor tissue. The capacity of NO production by NO-PB was measured, and the results showed the presence of NO in the culture medium from 4T1 cells incubated with NO-PB and inside the cells. NP-PB could be detected by photoacoustic imaging (PAI) in tumor tissue in 4T1 tumor bearing mice, suggesting this nanoparticle may serve as contrast agent for the noninvasive diagnosis of tumor tissues. NO-PB suppressed the growth of tissues in 4T1 tumor bearing mice. DOX-NO-PB showed more potent anti-tumor effects in 4T1 cells and tumor bearing mice compared with free DOX and NO-PB alone, indicating that the combination of DOX and NO-PB exhibited synergistic effects on tumor suppression.
Conclusion: This study provides a novel nanocarrier for gas therapy with additional PAI imaging capacity. This nanocarrier can be utilized for combination therapy of NO and chemotherapeutics which may serve as theranostic agents.

Keywords: gas therapy, nitric oxide, NO, photoacoustic imaging, PAI, sodium nitroprusside, SNP, hollow mesoporous Prussian blue (PB) nanoparticles


中文翻译：

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使用多柔比星负载和产生一氧化氮的空心普鲁士蓝纳米粒子的协同治疗，具有光声成像潜力抗乳腺癌

引言：传统​​的抗肿瘤化疗面临着巨大的挑战，如多药耐药（MDR）和对肿瘤组织的渗透性差。新出现的基于一氧化氮 (NO) 的气体疗法已被认为可降低 MDR 并改善对肿瘤组织的渗透。
方法：在本研究中，将产生 NO 的前药硝普钠 (SNP) 掺杂到中空介孔普鲁士蓝 (PB) 纳米颗粒中以制备产生 NO 的纳米颗粒 (NO-PB)，并进一步负载阿霉素 (DOX)。
结果：与中性 pH 相比，负载 DOX 的 NO-PB (DOX-NO-PB) 在 pH 6 时释放更快，表明 NO-PB 可能促进负载药物在酸性肿瘤组织中的释放。测量了 NO-PB 产生 NO 的能力，结果表明在与 NO-PB 一起孵育的 4T1 细胞的培养基中和细胞内部存在 NO。NP-PB 可以通过光声成像 (PAI) 在 4T1 荷瘤小鼠的肿瘤组织中检测到，表明这种纳米颗粒可以作为肿瘤组织无创诊断的造影剂。NO-PB 抑制 4T1 荷瘤小鼠组织的生长。与单独的游离 DOX 和 NO-PB 相比，DOX-NO-PB 在 4T1 细胞和荷瘤小鼠中显示出更有效的抗肿瘤作用，表明 DOX 和 NO-PB 的组合对肿瘤抑制具有协同作用。
结论：本研究为气体治疗提供了一种新型纳米载体，具有额外的 PAI 成像能力。这种纳米载体可用于 NO 和可作为治疗诊断剂的化疗药物的联合治疗。

关键词：气体疗法，一氧化氮，NO，光声成像，PAI，硝普钠，SNP，中空介孔普鲁士蓝（PB）纳米粒子