期刊
ACS NANO
卷 14, 期 1, 页码 347-359出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b05493
关键词
biofilm; nitric oxide; glutathione depletion; photodynamic therapy; synergy
类别
资金
- Science and Technology Planning Project of Zhejiang Province [2016C04002]
- Fundamental Research Funds for the Central Universities [2017XZZX001-03B]
- National Natural Science Foundation of China [21574114]
Biofilm has resulted in numerous obstinate clinical infections, posing severe threats to public health. It is urgent to develop original antibacterial strategies for eradicating biofilms. Herein, we develop a surface charge switchable supramolecular nanocarrier exhibiting pH-responsive penetration into an acidic biofilm for nitric oxide (NO) synergistic photodynamic eradication of the methicillin-resistant Staphylococcus aureus (MRSA) biofilm with negligible damage to healthy tissues under laser irradiation. Originally, by integrating the glutathione (GSH)-sensitive alpha-cyclodextrin (alpha-CD) conjugated nitric oxide (NO) prodrug (alpha-CD-NO) and chlorin e6 (Ce6) prodrug (alpha-CD-Ce6) into the pH-sensitive poly(ethylene glycol) (PEG) block polypeptide copolymer (PEG-(KLAKLAK)(2)-DA) via host-guest interaction, the supramolecular nanocarrier alpha-CD-Ce6-NO-DA was finely prepared. The supramolecular nanocarrier shows complete surface charge reversal from negative charge at physiological pH (7.4) to positive charge at acidic biofilm pH (5.5), promoting efficient penetration into the biofilm. Once infiltrated into the biofilm, the nanocarrier exhibits rapid NO release triggered by the overexpressed GSH in the biofilm, which not only produces abundant NO for killing bacteria but also reduces the biofilm GSH level to improve photodynamic therapy (PDT) efficiency. On the other hand, NO can react with reactive oxygen species (ROS) to produce reactive nitrogen species (RNS), further improving the PDT efficiency. Due to the effective penetration into the biofilm and depletion of biofilm GSH, the surface charge switchable GSH-sensitive NO nanocarrier can greatly improve the PDT efficiency at a low photosensitizer dose and laser intensity and cause negligible side effect to healthy tissues. Considering the above advantages, the strategy developed in this work may offer great possibilities to fight against biofilm infections.
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