2. Academic Validation
  3. M2 macrophage-mediated tigecycline nanoparticles for combating CRKP pneumonia via antibacterial and immunomodulatory therapy

M2 macrophage-mediated tigecycline nanoparticles for combating CRKP pneumonia via antibacterial and immunomodulatory therapy

  • J Control Release. 2026 May 10:393:114810. doi: 10.1016/j.jconrel.2026.114810.
Weijing Cheng 1,  Ling Wu 2,  Yu Liao 3,  Tingrui Zhang 2,  Xiujuan Han 4,  Zongguang Tai 2,  Quangang Zhu 2,  Zhongjian Chen 2,  Jing Tian 5,  Nan Ding 6,  Zhuo Wang 7
Affiliations

Affiliations

  • 1 Department of Pharmacy, The First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Shanghai 200433, China; School of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China.
  • 2 Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China.
  • 3 School of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China; Naval Medical Center of PLA, Naval Medical University, 338 West Huaihai Road, Shanghai 200052, China.
  • 4 Department of Pharmacy, The First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Shanghai 200433, China.
  • 5 Naval Medical Center of PLA, Naval Medical University, 338 West Huaihai Road, Shanghai 200052, China. Electronic address: [email protected].
  • 6 Department of Pharmacy, The First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Shanghai 200433, China. Electronic address: [email protected].
  • 7 Department of Pharmacy, The First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Shanghai 200433, China. Electronic address: [email protected].
PMID: 41819427 DOI: 10.1016/j.jconrel.2026.114810
Abstract

Pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) has a high mortality rate and exhibits multiple drug resistance, making current Antibacterial treatments of limited efficacy. To address the challenges of ineffective drug accumulation at the Infection site and excessive inflammation leading to tissue damage, this study developed a cell-based nano-bionic drug delivery system (denoted as PT@M2, PLGA-TIG nanoparticles loaded into M2 macrophages). This system encapsulates poly(lactic-co-glycolic acid) (PLGA) loaded with tigecycline within M2-type macrophages, thereby achieving stable circulation, rapid release in acidic microenvironments, and targeted delivery to the lungs. In vitro experiments showed that PT@M2 significantly reduced the minimum inhibitory concentration of CRKP, disrupted Bacterial membranes, and induced Reactive Oxygen Species accumulation. In a mouse pneumonia model, PT@M2 effectively reduced Bacterial colonies, alleviated inflammatory responses, and improved pulmonary histopathology. Wefurther confirmed that PT@M2 could inhibit calcium ion influx by downregulating CACNG6, thereby indirectly modulating the MAPK pathway. In summary, PT@M2 enhances Antibacterial efficacy through a dual mechanism of "bactericidal action + immune microenvironment remodeling," providing a novel therapeutic strategy for the treatment of multidrug-resistant Bacterial infections.

Keywords

Biomimetic nano-drug delivery system; Carbapenem-resistant Klebsiella pneumoniae (CRKP); M2 macrophages; Pneumonia; Tigecycline (TIG).

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