<br>膜靶向光敏剂在治疗念珠菌病中可防止耐药性并诱导免疫反应,Advanced Science

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膜靶向光敏剂在治疗念珠菌病中可防止耐药性并诱导免疫反应
Advanced Science ( IF 14.3 ) Pub Date : 2023-10-24 , DOI: 10.1002/advs.202207736
Ming-Yu Wu _{1,

2} , Xiaoyu Xu ₁ , Rui Hu _{1,

3} , Qingrong Chen ₁ , Luojia Chen ₁ , Yuncong Yuan ₁ , Jie Li ₄ , Li Zhou ₁ , Shun Feng ₂ , Lianrong Wang _{1,

3} , Shi Chen ₁ , Meijia Gu _{1,

3}

Affiliation

白色念珠菌 (C. albicans) 是人类普遍存在的多态性真菌，可引起不同类型的念珠菌病，包括口腔念珠菌病 (OC) 和外阴阴道念珠菌病 (VVC)，这些病会造成身心困扰，且造成经济损失。因此，开发替代抗真菌药物来防止耐药性并诱导免疫以消除念珠菌生物膜至关重要。在此，开发了一种新型膜靶向聚集诱导发射（AIE）光敏剂（PS）TBTCP-QY，用于念珠菌病的高效光动力疗法（PDT）。 TBTCP-QY具有高摩尔吸收系数和优异的生成 ¹ O ₂ 和·OH的能力，由于其高渗透性进入生物膜内部。此外，TBTCP-QY可以通过抑制白色念珠菌粘附（ALS3、EAP1和HWP1）、侵袭（SAP1和SAP2）和耐药（MDR1）相关基因的表达来有效抑制生物膜形成，这也是有利于消除潜在的真菌耐药性，治疗临床感染性疾病。 TBTCP-QY介导的PDT在小鼠模型体内有效靶向OC和VVC，诱导免疫反应，缓解炎症，并加速粘膜缺损的愈合，以对抗临床分离的氟康唑耐药菌株引起的感染。此外，TBTCP-QY表现出优异的生物相容性，表明其在OC和VVC的临床治疗中具有潜在的应用前景。

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A Membrane-Targeted Photosensitizer Prevents Drug Resistance and Induces Immune Response in Treating Candidiasis

Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane-targeted aggregation-induced emission (AIE) photosensitizer (PS), TBTCP-QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP-QY has a high molar absorption coefficient and an excellent ability to generate ¹O₂ and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP-QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion (ALS3, EAP1, and HWP1), invasion (SAP1 and SAP2), and drug resistance (MDR1) of C. albicans, which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP-QY-mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole-resistant strains. Moreover, TBTCP-QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.

更新日期：2023-10-24

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