期刊
JOURNAL OF CONTROLLED RELEASE
卷 344, 期 -, 页码 202-213出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.02.030
关键词
RGD; Liposome; Rapid phagocyte recognition; Intracellular bacterial infection; Methicillin-resistant Staphylococcus aureus (MRSA)
资金
- National Natural Science Foundation of China [82125035, 81973245, 81690263]
- Shanghai Education Commission Major Project [2021-01-07-00-07-E00081]
- Shanghai Natural Science Foundation [19431900300]
- Opening Project of Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry
- National Key R&D Program of China [2018YFC2002400]
- Sichuan Province, Jing'an District Health Research Project [2019MS03]
In this study, the in vivo fate and mechanism of cyclic RGD peptide functionalized liposome (cRGD-sLip) were investigated. It was found that cRGD-sLip demonstrated effective targeted drug delivery to bacteria-infected macrophages, improving the therapeutic efficacy of existing antibiotics in the treatment of intracellular bacterial infection.
RGD motif has long been exploited as a versatile tool for targeted drug delivery. However, there are so far no successful clinical translations of RGD functionalized nanomedicines. The lack of comprehensive understanding of their in vivo delivery process poses one of the main obstacles. As a reflection on cRGD-enabled targeting delivery, herein the in vivo fate of cyclic RGD peptide functionalized liposome (cRGD-sLip) and its fundamental mechanism are investigated. cRGD-sLip demonstrates incredibly rapid blood clearance and massive mononuclear phagocytic system (MPS) accumulation after intravenous injection. Phagocytes actively capture cRGD-sLip by recognizing alpha v beta 3 integrins and scavenger receptors, urging reinterrogation of RGD enabled targeting delivery. Intracellular infection with microbes invading and persisting in the phagocytic system poses serious threats to global public health. Most antimicrobial agents are unable to penetrate through host cell membrane and achieve optimal intracellular therapeutic concentration, resulting in ineffective bacterial killing. By leveraging the rapid phagocytic uptake, cRGD-sLip demonstrates the capability to facilitate effective targeted drug delivery to bac-teria infected macrophages and successfully reduce the bacterial burden in a murine intracellular Methicillin-resistant Staphylococcus aureus (MRSA) infection model, verifying the potential value of cRGD-sLip in improving therapeutic efficacy of existing antibiotics in the treatment of intracellular bacterial infection.
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