You Yanling,Yu Xu,Jiang Junjie,Chen Zhixin,Zhu Ya-Xuan,Chen Yihan,Lin Han,Shi Jianlin
Personalized synergistic antibacterial agents against diverse bacterial strains are receiving increasing attention in combating antimicrobial resistance. However, the current research has been struggling to strike a balance between strain specificity and broad-spectrum bactericidal activity. Here, we propose a bacterial cell wall-specific antibacterial strategy based on an in situ engineered nanocomposite consisting of carbon substrate and decorated TiO x dots, termed TiO x @C. The fiber-like carbon substrate of TiO x @C is able to penetrate the bacterial membrane of Pseudomonas aeruginosa ( P. aeruginosa ), but not that of Staphylococcus aureus ( S. aureu s) due to its thicker bacterial wall, thus achieving bacterial wall specificity. Furthermore, a series of experiments demonstrate the specific electro-mechanical co-sterilization effect of TiO x @C. On the one hand, TiO x @C can disrupt the electron transport chain and block the energy supply of S. aureus . On the other hand, TiO x @C capable of destroying the membrane structure of P. aeruginosa could cause severe mechanical damage to P. aeruginosa as well as inducing oxidative stress and protein leakage. In vivo experiments demonstrate the efficacy of TiO x @C in eliminating 97% of bacteria in wounds and promoting wound healing in wound-infected female mice. Overall, such a bacterial cell wall-specific nanomedicine presents a promising strategy for non-antibiotic treatments for bacterial diseases.
Bowen Deng,Rui Huang,Rui Liang,Yang Fei,Qing Luo,Guanbin Song
Altered tissue mechanics is vital for cancer development and malignancy, whether targeting the mechanical microenvironment could retard the initiation and progression of tumor is less explored. In this study, an orthotopic hepatocellular carcinoma (HCC) rat model was constructed to reproduce the mechanical and pathophysiological microenvironment of HCC development. LpMSN@CLG, a liver-targeted (L) and pH-sensitive (p) mesoporous silica nanoparticle (MSN) encapsulated with collagenase type-I (CLG), and DOX-LpMSN@CLG, on the basis of LpMSN@CLG, encapsulated with CLG and doxorubicin (DOX), were prepared to reduce matrix stiffness by degrading collagen in liver and HCC tumor. LpMSN@CLG, and DOX-LpMSN@CLG were respectively injected (i.v.) into rats at the stage of fibrosis and HCC, resulting in decreased collagen content in liver and HCC tissue, as well as reduced matrix stiffness. In addition, LpMSN@CLG treatment at the fibrosis stage retarded HCC initiation, and DOX-LpMSN@CLG treatment inhibited the growth of HCC tumor when compared with that of the rats treated by DOX alone, suggesting that reducing matrix stiffness in HCC tumor can improve the therapeutic efficacy of DOX. Taken together, our study demonstrated that mechanical intervention of tissue stiffness by CLG-loaded nanoparticles could retard the initiation and progression of HCC, suggesting the promising of mechanical intervention of hepatocellular carcinoma.
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