Figure 12.

(A) Schematic principle of bacterial toxin-triggered antibiotic release from gold nanoparticle stabilized liposomes to treat toxin-secreting bacteria. Vancomycin-loaded liposomes are protected by absorbing chitosan-coated gold nanoparticles (AuCHT) onto their surface to prevent them from fusing with one another or with bacterial membranes. Once the AuCHT-stabilized liposomes (AuCHT-liposome) encounter bacterial toxins, the toxins will form pores in the liposome membranes and thus release the encapsulated antibiotics, which subsequently kill or inhibit the growth of the bacteria that secrete the toxins. (B) The surface ζ potential (mV) of bare liposome (without AuCHT) and AuCHT-liposome with a liposome/AuCHT molar ratio of 1:300. Adapted with permission from Pornpattananangkul D, Zhang L, Olson S, et al. Bacterial toxin-triggered drug release from gold nanoparticle-stabilized liposomes for the treatment of bacterial infection. J Am Chem Soc. 2011;133(11):4132–4139. Copyright (2011) American Chemical Society.¹⁴² (C) Illustration of the synthesis of mixed-charge TMA/MUA nanoparticles. The relative compositions of these thiols in solution used for NP functionalization and on the resulting NPs are generally different, which is why the latter have to be determined independently by methods such as core etching followed by NMR. (D) Quantification of the NP charge polarities plotted against the composition of the mixed on-particle SAMs (composition expressed as XTMA:XMUA ratios as determined by core-etching/NMR analyses). The blue curve is for pH 11 and fully deprotonated MUAs; the red curve is for pH 7.4 (PBS buffer) under which conditions a small fraction of the MUAs is protonated (and hence the curve shifts slightly upwards compared to the one for pH 11). Error bars are based on three separate measurements. (E) Microscopic studies of bacteria treated with different types of mixed-charge NPs. Scanning electron microscopy (SEM) images of E. coli incubated with i) pure-MUA and ii) pure-TMA NPs. Inset in (B) shows TMA NPs adsorbing on the bacteria. For TEM images resolving the individual NPs. iii) Kelvin force microscopy (KFM) image of an E. coli bacterium illustrating its net negative surface potential of about 50 mV (blue horizontal line). iv) SEM, v) TEM, and vi) AFM images of E. coli after incubation with cTMA:cMUA=80:20 AuNPs evidencing the rupture of the bacterial cell wall. vii) TEM image showing cTMA:cMUA=80:20 AuNPs (small dark dots) associated with the intracellular material leaked from the bacterium upon lysis. Adapted from Angewandte Chemie International Edition, Vol 55/ Issue 30, Pillai PP, Kowalczyk B, Kandere-Grzybowska K, Borkowska M, Grzybowski BA, Engineering gram selectivity of mixed-charge gold nanoparticles by tuning the balance of surface charges, Pages No.8610–8614, Copyright (2016), with permission from John Wiley and Sons. © 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.¹⁴³