Polymersomes Eradicating Intracellular Bacteria

Federico Fenaroli, James D. Robertson, Edoardo Scarpa, Virginia M. Gouveia, Claudia Di Guglielmo, Cesare De Pace, Philip M. Elks, Alessandro Poma, Dimitrios Evangelopoulos, Julio Ortiz Canseco, Tomasz K. Prajsnar, Helen M. Marriott, David H. Dockrell, Simon J. Foster, Timothy D. Mchugh, Stephen A. Renshaw, Josep Samitier Martí, Giuseppe Battaglia, Loris Rizzello

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Mononuclear phagocytes such as monocytes,tissue-specific macrophages, and dendritic cells are primaryactors in both innate and adaptive immunity. These profes-sional phagocytes can be parasitized by intracellular bacteria,turning them from housekeepers to hiding places and favoringchronic and/or disseminated infection. One of the mostinfamous is the bacteria that cause tuberculosis (TB), whichis the most pandemic and one of the deadliest diseases, withone-third of the world’s population infected and an average of1.8 million deaths/year worldwide. Here we demonstrate theeffective targeting and intracellular delivery of antibiotics toinfected macrophages bothin vitroandin vivo, using pH-sensitive nanoscopic polymersomes made of PMPC−PDPA block copolymer. Polymersomes showed the ability tosignificantly enhance the efficacy of the antibiotics killingMycobacterium bovis,Mycobacterium tuberculosis, and anotherestablished intracellular pathogen,Staphylococcus aureus. Moreover, they demonstrated to easily access TB-like granulomatissuesone of the harshest environments to penetratein zebrafish models. We thus successfully exploited this targeting forthe effective eradication of several intracellular bacteria, includingM. tuberculosis, the etiological agent of human TB



Original languageEnglish
Pages (from-to)8287-8298
JournalACS Nano
Volume14
Issue number7
DOIs
Publication statusPublished - 28 Jul 2020

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