2. Academic Validation
  3. cRGD enables rapid phagocytosis of liposomal vancomycin for intracellular bacterial clearance

cRGD enables rapid phagocytosis of liposomal vancomycin for intracellular bacterial clearance

  • J Control Release. 2022 Apr;344:202-213. doi: 10.1016/j.jconrel.2022.02.030.
Guanghui Li 1,  Mengke Wang 2,  Tianhao Ding 3,  Jing Wang 4,  Tao Chen 5,  Qianwen Shao 2,  Kuan Jiang 3,  Liping Wang 5,  Yifei Yu 3,  Feng Pan 2,  Bin Wang 6,  Xiaoli Wei 7,  Jun Qian 8,  Changyou Zhan 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 201203, PR China; Department of Pharmacy, Jing'an District Central Hospital of Shanghai, Shanghai 200040, PR China.
  • 2 School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 201203, PR China.
  • 3 Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, PR China.
  • 4 Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
  • 5 Department of Pharmacy, Jing'an District Central Hospital of Shanghai, Shanghai 200040, PR China.
  • 6 School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 201203, PR China; Department of Pharmacy, Jing'an District Central Hospital of Shanghai, Shanghai 200040, PR China. Electronic address: wangbin@huashan.org.cn.
  • 7 Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, PR China. Electronic address: xlwei@fudan.edu.cn.
  • 8 School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 201203, PR China. Electronic address: qianjun@fudan.edu.cn.
PMID: 35235809 DOI: 10.1016/j.jconrel.2022.02.030
Abstract

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 αvβ3 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 bacteria 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.

Keywords

Intracellular bacterial infection; Liposome; Methicillin-resistant Staphylococcus aureus (MRSA); RGD; Rapid phagocyte recognition.

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