Department of pharmacy, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China.
Department of physics, Northwest University of Technology, Xi'an, 710032, Shaanxi Province, China.
Theranostics. 2020 Mar 26;10(11):4795-4808. doi: 10.7150/thno.42922. eCollection 2020.
: Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. : Herein, a novel acid-responsive superporogen and photosensitizer (SiO-P) was developed. Because of the protonation of the photosensitizer and the high binding energy of the polyionic liquid, SiO-P changed to positive SiO-P in an acidic microenvironment of biofilm infection. SiO-P could combine with negatively charged extracellular polymeric substances (EPS) and create holes to remove the biofilm barrier. To strengthen the interaction between SiO-P and EPS, SiO-P of high charge density was prepared by grafting the high-density initiation site of ATRP onto the surface of the SiO base. : Due to the rapid protonation rate of COO and the strong binding energy of SiO-P with EPS, SiO-P could release 90% of Ce6 in 10 s. With the stronger electrostatic and hydrophobic interaction of SiO-P with EPS, the surface potential, hydrophobicity, adhesion and mechanical strength of biofilm were changed, and holes in the biofilm were created in 10 min. Combining with the release of photosensitizers and the porous structure of the biofilm, Ce6 was efficiently concentrated in the biofilm. The and antibacterial experiments proved that SiO-P dramatically improved the PDT efficacy against MRSA biofilm infection. : These findings suggest that SiO-P could rapidly increase the concentration of photosensitizer in biofilm and it is an effective therapy for combating biofilm infection.
生物膜感染导致的多重耐药菌感染很难用传统疗法消除。光动力疗法(PDT)是一种对抗生物膜感染的有效抗菌方法。然而,生物膜外的受阻光敏剂极大地限制了 PDT 的疗效。
本文开发了一种新型的酸响应超增塑剂和光敏剂(SiO-P)。由于光敏剂的质子化和聚离子液体的高结合能,SiO-P 在生物膜感染的酸性微环境中转变为带正电的 SiO-P。SiO-P 可以与带负电荷的细胞外聚合物(EPS)结合,并产生孔来去除生物膜屏障。为了增强 SiO-P 与 EPS 的相互作用,通过在 SiO 基底表面接枝 ATRP 的高密度引发点,制备了具有高电荷密度的 SiO-P。
由于 COO 的快速质子化速率和 SiO-P 与 EPS 的强结合能,SiO-P 在 10 s 内可以释放 90%的 Ce6。由于 SiO-P 与 EPS 具有更强的静电和疏水性相互作用,生物膜的表面电位、疏水性、粘附力和机械强度发生了变化,在 10 min 内生物膜上产生了孔。结合光敏剂的释放和生物膜的多孔结构,Ce6 被有效地集中在生物膜中。抗菌实验证明,SiO-P 显著提高了 PDT 对耐甲氧西林金黄色葡萄球菌(MRSA)生物膜感染的疗效。
这些发现表明,SiO-P 可以快速增加生物膜中光敏剂的浓度,是一种有效的治疗生物膜感染的方法。