Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China; Research Center for Intelligent Sensing, Zhejiang Lab, Hangzhou 310000, China.
Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.
Acta Biomater. 2021 Sep 1;131:544-554. doi: 10.1016/j.actbio.2021.07.018. Epub 2021 Jul 13.
Diabetic wound healing is highly desirable but remains a great challenge owing to the continuous damage of excess reactive oxygen species (ROS) and degradation of therapeutic peptide drugs by over-expressed matrix metalloproteinase (MMP). Herein, we developed a stimuli-responsive smart dressing for theranostics of diabetic wounds using graphene quantum dots-decorated luminescent porous silicon (GQDs@PSi), which was further loaded with peptide and embedded in chitosan (CS) film. The confinement of GQDs in nanochannels of PSi endowed GQDs@PSi with efficient fluorescence resonance energy transfer (FRET) effect, leading to initial red fluorescence of PSi with complete quench of GQD's blue fluorescence. Furthermore, the decoration of GQDs on PSi surface significantly enhanced the loading capacity for peptide drugs including epidermal growth factor (EGF) and insulin (Ins) which can promote diabetic wounds healing. The peptides coloaded in GQDs@PSi exhibited sustained release behavior and could be protected in presence of MMP owing to size exclusion of PSi's nanochannels. As HO-triggered oxidation of PSi lead to weakened FRET effect and degradation of PSi, GQDs@PSi demonstrated HO-responsive ratiometric fluorescence change (from red PSi to blue GQDs) and drug release behavior. In combination with CS's degradation in the acidic and oxidation microenvironment, the smart dressing also showed stimuli-responsive drug release toward slightly acid and highly oxidative conditions in diabetic wounds. In vitro and in vivo results demonstrated the smart dressing enhanced the proliferation and migration of cells as well as significantly healed diabetic wounds. Real-time indicating of the exacerbation or healing of diabetic wounds was also realized using the rate of fluorescent discoloration of the dressing. STATEMENT OF SIGNIFICANCE: In this work, a dual luminescent nanomaterial was created by hosting graphene quantum dots (GQDs) in the nanochannel of porous silicon (PSi), which was further applied for theranostics of diabetic wound. The synergistic effect of the host-guest nanohybrid is significant. The GQDs can significantly improve the capacity for peptide drug loading and form a stimuli-response visual ratiometric sensor with luminescent PSi, which can also protect and sustain release of peptide drugs for effective diabetic wounds treatment. After embedded in a chitosan film, the smart dressing displayed HO-responsive visual ratiometric fluorescence change and drug release behavior. In vitro and in vivo results demonstrated the smart dressing enhanced the proliferation and migration of cells as well as significantly healed diabetic wounds.
糖尿病创面愈合是非常理想的,但由于过量活性氧(ROS)的持续损伤和过度表达的基质金属蛋白酶(MMP)对治疗性肽药物的降解,这仍然是一个巨大的挑战。在此,我们使用石墨烯量子点修饰的发光多孔硅(GQDs@PSi)开发了一种用于糖尿病创面治疗的刺激响应智能敷料,其进一步负载肽并嵌入壳聚糖(CS)膜中。GQDs 在 PSi 的纳米通道中的限制赋予了 GQDs@PSi 高效的荧光共振能量转移(FRET)效应,导致 PSi 的初始红色荧光完全猝灭了 GQD 的蓝色荧光。此外,GQDs 修饰在 PSi 表面上显著提高了包括表皮生长因子(EGF)和胰岛素(Ins)在内的肽药物的载药量,从而促进糖尿病创面愈合。在 MMP 存在下,共装载在 GQDs@PSi 中的肽药物表现出持续释放行为,并能得到保护,这是由于 PSi 的纳米通道的尺寸排阻作用。由于 PSi 的 HO 触发氧化导致 FRET 效应减弱和 PSi 的降解,因此 GQDs@PSi 表现出 HO 响应的比率荧光变化(从红色 PSi 到蓝色 GQDs)和药物释放行为。结合 CS 在酸性和氧化微环境中的降解,智能敷料也表现出对糖尿病创面中轻微酸性和高度氧化条件的刺激响应药物释放。体外和体内结果表明,智能敷料促进了细胞的增殖和迁移,并显著治愈了糖尿病创面。还可以通过敷料的荧光变色率来实现对糖尿病创面恶化或愈合的实时指示。
在这项工作中,通过将石墨烯量子点(GQDs)封装在多孔硅(PSi)的纳米通道中,创建了一种双荧光纳米材料,进一步将其应用于糖尿病创面的治疗。这种主体-客体纳米杂化材料的协同效应非常显著。GQDs 可以显著提高肽药物的载药能力,并与发光 PSi 形成刺激响应的可视比率传感器,还可以保护和持续释放肽药物,从而有效治疗糖尿病创面。将其嵌入壳聚糖膜中后,智能敷料表现出 HO 响应的可视比率荧光变化和药物释放行为。体外和体内结果表明,智能敷料促进了细胞的增殖和迁移,并显著治愈了糖尿病创面。