A Facile Coordination Polymer Nanoparticle for Sonodynamic Therapy Combating Drug-Resistant Bacteria

Abstract

The emergence of drug resistance in bacteria, along with the protective nature and intricate environment of biofilms, impedes the effective treatment of severe bacterial infections, posing significant health risks. Herein, a coordination polymer nanoparticle (LZC) is fabricated via a facile in situ strategy for sonodynamic therapy (SDT) combating drug-resistant bacteria-induced infections. By conjugating the Food and Drug Administration (FDA)-approved safe sonosensitizer porphyrin chlorin e6 (Ce6) with a positively charged antimicrobial peptide LL37 through coordination interaction, the resultant LZC exhibits uniform size and a positively charged surface, which is beneficial for the efficient capture of bacteria and improved nanoparticle penetration into biofilms. Under ultrasound (US) stimuli, the nanoparticle generates a higher reactive oxygen species (ROS) compared with the free sonosensitizers, as well as the production of heat, leading to bacterial cell death and biofilm disruption. In vitro evaluations reveal the robust antibacterial activity of LZC, achieving up to 99% eradication of multi-drug resistant Pseudomonas aeruginosa (MDRPA) and significant biofilm eradication under deep-penetrating US irradiation. Moreover, the establishment of coordination polymer nanoparticles represents an innovative strategy to enhance SDT in an MDRPA-induced-pneumonia mice model and provides a great promise for advancing therapeutic interventions in deep tissue bacterial infections.