PDF(Pubmed)
Abstract：
Introduction: Dexamethasone (DEX), as an important enduring-effect glucocorticoid (GC), holds great promise in the field of lung ischemia-reperfusion injury (LIRI) comprehensive therapy owing to its immunomodulatory properties, such as inducing apoptosis and cell cycle distribution. However, its potent anti-inflammatory application is still restricted because of multiple internal physiologic barriers. Methods: Herein, we developed upconversion nanoparticles (UCNPs) coated with photosensitizer/capping agent/fluorescent probe-modified mesoporous silica (UCNPs@mSiO2[DEX]-Py/β-CD/FITC, USDPFs) for precise DEX release synergistic LIRI comprehensive therapy. The UCNPs were designed by covering an inert YOF:Yb shell on the YOF:Yb, Tm core to achieve high-intensity blue and red upconversion emission upon Near-Infrared (NIR) laser irradiation. Results: Under suitable compatibility conditions, the molecular structure of photosensitizer can be damaged along with capping agent shedding, which endowed USDPFs with an outstanding capability to carry out DEX release controlling and fluorescent indicator targeting. Furthermore, the hybrid encapsulating of DEX significantly increased utilization of nano-drugs, improving the water solubility and bioavailability, which was conducive to developing the anti-inflammatory performance of USDPFs in the complex clinical environment. Discussion: The response-controlled release of DEX in the intrapulmonary microenvironment can reduce normal cell damage, which can effectively avoid the side effects of nano-drugs in anti-inflammatory application. Meanwhile, the multi-wavelength of UCNPs endowed nano-drugs with the fluorescence emission imaging capacity in an intrapulmonary microenvironment, providing precise guidance for LIRI.
摘要：
简介：地塞米松（DEX），作为一种重要的持久效应糖皮质激素（GC），由于其免疫调节特性，在肺缺血再灌注损伤（LIRI）综合治疗领域具有广阔的前景，如诱导细胞凋亡和细胞周期分布。然而,由于多种内部生理障碍，其有效的抗炎应用仍然受到限制。方法：这里，我们开发了涂覆有光敏剂/封端剂/荧光探针修饰的介孔二氧化硅（UCNPs@mSiO2[DEX]-Py/β-CD/FITC，USDPFs）用于精确的DEX释放协同LIRI综合治疗。UCNP是通过在YOF：Yb上覆盖惰性YOF：Yb外壳来设计的，Tm核心在近红外(NIR)激光照射下实现高强度蓝色和红色上转换发射。结果:在适宜的配伍条件下,光敏剂的分子结构会随着封端剂的脱落而受损，这赋予了USDPF进行DEX释放控制和荧光指示剂靶向的杰出能力。此外，DEX的混合封装显着提高了纳米药物的利用率，提高水溶性和生物利用度，这有利于开发USDPFs在复杂临床环境中的抗炎性能。讨论:DEX在肺内微环境中的反应控制释放可减少正常细胞损伤,能有效避免纳米药物在抗炎应用中的副作用。同时,多波长UCNPs赋予纳米药物在肺内微环境中的荧光发射成像能力,为LIRI提供精确的指导。
