Synergistic antibacterial and biofilm eradication activity of quaternary-ammonium compound with copper ion.

Antibiotics overuse and misuse increase the emergence of multidrug-resistant bacterial strains, which often leads to the failure of conventional antibiotic therapies. Even worse, the tendency of bacteria to form biofilms further increases the therapeutic difficulty, because the extracellular matrix prevents the penetration of antibiotics and triggers bacterial tolerance. Therefore, developing novel antibacterial agents or therapeutic strategies with diverse antibacterial mechanisms and destruction of bacteria biofilm is a promising way to combat bacterial infections. In the present study, the combination of quaternary ammonium compound poly(diallyl dimethyl ammonium chloride) (PDDA) with Cu2+ was screened out to fight common pathogenic Staphylococcus aureus (S. aureus) through multi-mechanisms. This combination appeared strong synergistic antibacterial activity, and the fractional inhibitory concentration index was as low as 0.032. The synergistic antibacterial mechanism involved the destruction of the membrane function, generation of intracellular reactive oxygen, and promotion more Cu2+ into the cytoplasm. Further, the combination of PDDA and Cu2+ reduced the extracellular polysaccharide matrix, meanwhile killing the bacteria embedded in the biofilm. The biocompatibility study in vitro revealed this combination exhibited low cytotoxicity and hemolysis ratio even at 8 times of minimum bactericidal concentration. This work provides a novel antibacterial agents combination with higher efficiency to fight planktonic and biofilm conditions of S. aureus.

Construction of small-sized superparamagnetic Janus nanoparticles and their application in cancer combined chemotherapy and magnetic hyperthermia.

Novel Janus nanoparticles (J-NPs) are developed by using single iron oxide (Fe3O4) nanoparticles as the core and hydrophobic/hydrophilic polymeric brushes as the cloak. Because of the superparamagnetism and asymmetric functionality of J-NPs, they are used as drug carriers and therapeutic agents for cancer chemotherapy and magnetic hyperthermia with a magnetic resonance imaging (MRI) guide. The asymmetric functionality is constituted of hydrophobic polymethyl methacrylate (PMMA) brushes and hydrophilic polyacrylic acid (PAA) brushes, which are 'grafting to' or 'grafting from' Fe3O4 nanoparticles via activators regenerated by electron transfer atom transfer radical polymerization. The terminal chains of PMMA and PAA brushes are coordinated with Fe3O4 nanoparticles, so PMMA/Fe3O4/PAA J-NPs possess structural stability in solvents. Because of the brush-structure, PMMA/Fe3O4/PAA J-NPs show high encapsulation efficiency (89.75 ± 2.35%) and loading capacity (8.95 ± 0.26%). Under the alternating magnetic field (AMF), drug-loaded J-NPs achieve the highest cell proliferation-inhibition ratio in the cell proliferation test in vitro and the tumor growth inhibition test in vivo compared to single chemotherapy or magnetic hyperthermia. Meanwhile, J-NPs show good T2 imaging.