Issue 18, 2022

Core–shell polycationic polyurea pharmadendrimers: new-generation of sustainable broad-spectrum antibiotics and antifungals

Abstract

The efficacy of conventional antimicrobials is falling to critical levels and raising alarming concerns around the globe. In this scenery, engineered nanoparticles emerged as a solid strategy to fight growing deadly infections. Here, we show the in vitro and in vivo performance of pharmadendrimers, a novel class of engineered polyurea dendrimers that are synthetic mimics of antibacterial peptides, against a collection of both Gram-positive and Gram-negative bacteria and fungi. These nanobiomaterials are stable solids prepared by low-cost and green processes, display a dense positively charged core–shell, and are biocompatible and hemocompatible drugs. Mechanistic data, corroborated by coarse-grained molecular dynamics simulations, points towards a fast-killing mechanism via membrane disruption, triggered by electrostatic interactions. Altogether this study provides strong evidence and support for the future use of polyurea pharmadendrimers in antibacterial and antifungal nanotherapeutics.

Graphical abstract: Core–shell polycationic polyurea pharmadendrimers: new-generation of sustainable broad-spectrum antibiotics and antifungals

Supplementary files

Article information

Article type
Paper
Submitted
02 May 2022
Accepted
12 Jul 2022
First published
22 Jul 2022

Biomater. Sci., 2022,10, 5197-5207

Core–shell polycationic polyurea pharmadendrimers: new-generation of sustainable broad-spectrum antibiotics and antifungals

S. N. Pinto, D. Mil-Homens, R. F. Pires, M. M. Alves, G. Serafim, N. Martinho, M. Melo, A. M. Fialho and V. D. B. Bonifácio, Biomater. Sci., 2022, 10, 5197 DOI: 10.1039/D2BM00679K

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