Drug resistance and side effects are the two main problems of chemotherapy. In order to address these big challenges, p-PB@d-SiO₂, which has the ability to co-deliver both the hydrophobic drug doxorubicin hydrochloride (DOX) and the hydrophilic drug ibuprofen (IBU), is constructed to achieve synergistic treatment. The drug-loaded nanoparticle consists of porous Prussian blue (p-PB) as the core and dendrimer-like SiO₂ (d-SiO₂) as the shell, which is further thiolated and coated with polyethylene glycol thiol (HS-PEG) to form the “Dual-Key-and-Lock” drug carrier p-PB@d-SiO₂-SS-PEG. The locked drugs can only be released in the presence of cooperative triggers, i.e., a high glutathione concentration (the first key) and an acidic environment (the second key). The “dual key”-triggered release is much more significant in cancer lesions than in normal tissues, reducing side effects. Furthermore, cell viability experiments highlight the superior therapeutic efficacy of the dual-drug-loaded nanoparticles compared with the single-drug systems (60%, 73% and 86% vs. 56%, 68%, and 76% at 100, 200 and 500 μg mL⁻¹, respectively). In vitro and in vivo experiments demonstrate the potential application of p-PB@d-SiO₂-SS-PEG for dual-mode fluorescence and magnetic-resonance-imaging-guided chemo-photothermal therapy. The “Dual-Key-and-Lock” drug carrier system exhibits the “1 + 1 > 2” effect, demonstrating its excellent performance in synergy therapy for improved therapeutic efficiency and thereby reducing conventional drug resistance and side effects.

中文翻译：

---

“双键锁定”双药载体，用于双模式成像引导的化学光热疗法

耐药性和副作用是化疗的两个主要问题。为了解决这些巨大的挑战，构建了能够共同递送疏水性药物阿霉素盐酸盐（DOX）和亲水性药物布洛芬（IBU）的能力的p-PB @ d-SiO ₂来实现协同治疗。载有药物的纳米颗粒由多孔的普鲁士蓝（p-PB）作为核和树状的类SiO ₂（d-SiO ₂）作为壳组成，将其进一步硫醇化并用聚乙二醇硫醇（HS-PEG）包覆形成“双键锁定”药物载体p-PB @ d-SiO ₂ -SS-PEG。锁定的药物只能在存在协同触发的情况下释放，即，高谷胱甘肽浓度（第一键）和酸性环境（第二键）。在癌症病变中，“双重关键”触发的释放比在正常组织中更为重要，从而减少了副作用。此外，细胞活力实验凸显了与单药系统相比，双药负载的纳米颗粒具有更好的治疗效果（分别在100、200和60℃时分别为60％，73％和86％， 56％，68％和76％）。分别为500μgmL ^-1）。体外和体内实验证明了p-PB @ d-SiO ₂的潜在应用-SS-PEG用于双模式荧光和磁共振成像引导的化学光热疗法。“双键锁定”药物载体系统表现出“ 1 + 1> 2”效应，证明了其在协同治疗中的出色性能，可提高治疗效率，从而降低传统的耐药性和副作用。