Mucus-Permeable Sonodynamic Therapy Mediated Amphotericin B-Loaded PEGylated PLGA Nanoparticles Enable Eradication of Candida albicans Biofilm

作者全名："Yang, Min; Xie, Mengyao; Guo, Jiajun; Zhang, Yuqing; Qiu, Yan; Wang, Zhibiao; Du, Yonghong"

作者地址："[Yang, Min; Xie, Mengyao; Guo, Jiajun; Zhang, Yuqing; Qiu, Yan; Wang, Zhibiao; Du, Yonghong] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China; [Yang, Min; Xie, Mengyao; Guo, Jiajun; Zhang, Yuqing; Qiu, Yan; Wang, Zhibiao; Du, Yonghong] Chongqing Med Univ, Chongqing Key Lab Biomed Engn, Chongqing 400016, Peoples R China"

通信作者："Wang, ZB; Du, YH (通讯作者)，Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001134520700001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：18

期号：　

开始页：7941

结束页：7963

文献类型：Article

关键词：C. albicans biofilm; PEGylated nanoparticles; mucus penetration; sonodynamic therapy

摘要："Background: Candida albicans (C. albicans) forms pathogenic biofilms, and the dense mucus layer secreted by the epithelium is a major barrier to the traditional antibiotic treatment of mucosa-associated C. albicans infections. Herein, we report a novel antibiofilm strategy of mucus-permeable sonodynamic therapy (mp-SDT) based on ultrasound (US)-mediated amphotericin B-loaded PEGylated PLGA nanoparticles (AmB-NPs) to overcome mucus barrier and enable the eradication of C. albicans biofilm. Methods: AmB-NPs were fabricated using ultrasonic double emulsion method, and their physicochemical and sonodynamic properties were determined. The mucus and biofilm permeability of US-mediated AmB-NPs were further investigated. Moreover, the antibiofilm effect of US-mediated AmB-NPs treatment was thoroughly evaluated on mucus barrier abiotic biofilm, epithelium-associated biotic biofilm, and C. albicans-induced rabbit vaginal biofilms model. In addition, the ultrastructure and secreted cytokines of epithelial cells and the polarization of macrophages were analyzed to investigate the regulation of local cellular immune function by US-mediated AmB-NPs treatment. Results: Polymeric AmB-NPs display excellent sonodynamic performance with massive singlet oxygen (1O2) generation. US-mediated AmB-NPs could rapidly transport through mucus and promote permeability in biofilms, which exhibited excellent eradicating ability to C. albicans biofilms. Furthermore, in the vaginal epithelial cells (VECs)-associated C. albicans biofilm model, the mp-SDT scheme showed the strongest biofilm eradication effect, with up to 98% biofilm re-formation inhibition rate, improved the ultrastructural damage, promoted local immune defense enhancement of VECs, and regulated the polarization of macrophages to the M1 phenotype to enhance macrophageassociated antifungal immune responses. In addition, mp-SDT treatment exhibited excellent therapeutic efficacy against C. albicansinduced rabbit vaginitis, promoted the recovery of mucosal epithelial ultrastructure, and contributed to the reshaping of a healthier vaginal microbiome. Conclusion: The synergistic anti-biofilm strategies of mp-SDT effectively eradicated C. albicans biofilm and simultaneously regulated local antifungal immunity enhancement, which may provide a new approach to treat refractory drug-resistant biofilmassociated mucosal candidiasis."

基金机构：Chongqing Natural Science Foundation Project [CSTB2022NSCQ-MSX0124]; Chongqing Graduate Student Research Innovation Project [CYB22223]

基金资助正文："This study was supported by the Chongqing Natural Science Foundation Project [No. CSTB2022NSCQ-MSX0124] , and Chongqing Graduate Student Research Innovation Project [No. CYB22223] ."