發明
中華民國
109110896
I 770489
碳量子點及其用途
國立臺灣海洋大學
2022/07/11
我們利用二步合成的方式將亞精胺修飾在檸檬酸銨所合成的碳奈米量子點 (Spd–CQDs),第一步碳奈米量子點 (CQDSpds) 是藉由檸檬酸銨在固態下熱裂解形成,第二步再與亞精胺簡單鍛燒處理所製備Spd–CQDs可以做為抗菌劑。合成的Spd–CQDs大小約 4.6 nm對大腸桿菌、綠膿桿菌、金黃色葡萄球菌及枯草芽孢桿菌最小抑菌濃度皆比亞精胺低 (約25000倍低)。為了確認其生物相容性,我們分別利用兔子角膜基質細胞進行生物相容性測試、溶血實驗測試、體內生物相容性測試,結果顯示,當CQDSpds之濃度為50 μg/mL (約MIC之10倍) 時,細胞仍有90%以上存活,且此濃度亦不會造成血球破裂。於眼內,注入 100 μg/mL之CQDSpds,並未造成組織反應,顯示此材料具有良好的生物相容性。動物實驗我們進行了大鼠傷口感染多重抗藥性金黃色葡萄球菌 (MRSA) 後,觀察結果得知Spd–CQDs的抗菌與促進傷口癒合效果非常好。另一方面,於兔子細菌角膜炎模式中,比較CQDSpds與商化眼藥水之治療效果,發現CQDSpds具有良好的治療效果,且所需濃度較商化眼藥水低10倍,可降低給予高濃度給藥造成副作用之風險。 We report a two-step method to synthesize spermidine-capped fluorescent carbon quantum dots (Spd–CQDs) and their potential application as an antibacterial agent. Fluorescent carbon quantum dots (CQDSpds) were synthesized by pyrolysis of ammonium citrate in the solid state, and then modified with spermidine by a simple heating treatment without a coupling agent. The antimicrobial activity of the as-synthesized Spd–CQDs (size ~4.6 nm) was tested against non-multidrug resistant E. coli, S. aureus, B. subtilis, and P. aeruginosa bacteria and also multidrug-resistant bacteria, methicillin-resistant S. aureus (MRSA). The minimal inhibitory concentration value of Spd–CQDs was much lower (>25,000-fold) than that of spermidine. To evaluate the in vitro biocompatibility of CQDSpds, we studied their cytotoxicity and hemolysis effects toward RCK cells [rabbit corneal keratocytes (RCKs)] and human red blood cells (RBCs), respectively. After incubation with CQDSpds at concentrations up to 50 μg mL−1 (>10-fold MIC for tested bacteria), the CQDSpds showed negligible cytotoxicity toward RCK cells versus untreated cells. The hemolysis assay was performed in defibrinated human blood to show the harmlessness of the CQDSpds to RBCs at concentrations up to 100 μg mL−1 in biological solution. In vivo ocular biocompatibility of nanomaterials is crucial for their success in ophthalmic applications, herein we examined the anterior segment tissue responses to intrastromally administered CQDSpds (20 μL, 100 μg mL−1). Our results clearly demonstrated that the intrastromally administered CQDSpds were highly biocompatible and did not initiate a tissue response. To demonstrate its practical application, we conducted in vivo MRSA-infected wound healing studies in rats, which showed faster healing, better epithelialization and formation of collagen fibers when Spd–CQDs were used as a dressing material. Furthermore, topical administration of CQDSpds as a medication showed much superior efficacy in BK treatment compared to Ag NPs and commercial eye drops (at same concentration).
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