Eradication of Multidrug-Resistant Staphylococcal
Infections by Light-Activatable Micellar Nanocarriers in a Murine Model
Liu, Y (Liu, Yong)[ 1,2,3 ] ; van der Mei, HC (van der Mei, Henny C.)[ 2,3 ] ; Zhao, BR (Zhao, Bingran)[ 4,5 ] ; Zhai, Y (Zhai, Yan)[ 1 ] ; Cheng, TJ (Cheng, Tangjian)[ 1 ] ; Li, YF (Li, Yuanfeng)[ 1 ] ; Zhang, ZK (Zhang, Zhenkun)[ 1 ] ; Busscher, HJ (Busscher, Henk J.)[ 2,3 ] ; Ren, YJ (Ren, Yijin)[ 4,5 ] ; Shi, LQ (Shi, Linqi)[ 1 ]
ADVANCED
FUNCTIONAL MATERIALS, 2017, 27(44): 文献号: 1701974
DOI: 10.1002/adfm.201701974
WOS:000416035400001
Abstract
Bacterial
infections are mostly due to bacteria in their biofilm mode-of-growth, making
them recalcitrant to antibiotic penetration. In addition, the number of
bacterial strains intrinsically resistant to available antibiotics is
alarmingly growing. This study reports that micellar nanocarriers with a
poly(ethylene glycol) shell fully penetrate staphylococcal biofilms due to
their biological invisibility. However, when the shell is complemented with
poly(beta-amino ester), these mixed-shell micelles become positively charged in
the low pH environment of a biofilm, allowing not only their penetration but
also their accumulation in biofilms without being washed out, as do
single-shell micelles lacking the pH-adaptive feature. Accordingly, bacterial
killing of multidrug resistant staphylococcal biofilms exposed to
proto-porphyrin IX-loaded mixed-shell micelles and after light-activation is
superior compared with single-shell micelles. Subcutaneous infections in mice,
induced with vancomycin-resistant, bioluminescent staphylococci can be
eradicated by daily injection of photoactivatable protoporphyrin IX-loaded,
mixed-shell micelles in the bloodstream and light-activation at the infected
site. Micelles, which are not degraded by bacterial enzymes in the biofilm, are
degraded in the liver and spleen and cleared from the body through the kidneys.
Thus, adaptive micellar nanocarriers loaded with light-activatable
antimicrobials constitute a much-needed alternative to current antibiotic
therapies.
