Alginate lyase immobilized Chlamydomonas algae microrobots: minimally invasive therapy for biofilm penetration and eradication
Xiaoting Zhang, Huaan Li, Lu Liu, Yanzhen Song, Lishan Zhang, Jiajun Miao, Jiamiao Jiang, Hao Tian, Chang Liu, Fei Peng, Yingfeng Tu
Abstract
Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo , showing huge promise for the active treatment of biofilm-associated infections. Self-propelled CR@Alg microrobots penetrate and eliminate medical device-associated biofilms by disrupting the three-dimensional structure of the matrix and generating ROS to damage bacteria.