A research team from Southwest University, led by Professor Lei Luo, has reported a hemoglobin-based nanoparticle (TIG-HBNP) in BME Frontiers that precisely delivers the antibiotic tigecycline (TIG) to infection sites caused by Klebsiella pneumoniae , presenting a novel strategy to tackle multidrug-resistant pneumonia.
K. pneumoniae is a major cause of severe pneumonia, and TIG is often regarded as a "last-resort" antibiotic for treating such infections. However, TIG's widespread distribution throughout the body results in low concentrations in the lungs—where the infection occurs—and dose-limiting toxicity, hindering its clinical effectiveness. To address this challenge, the researchers leveraged the bacterium's dependence on iron: hemoglobin (HB), a protein rich in iron, is naturally taken up by K. pneumoniae , making it an ideal targeting carrier for TIG.
The TIG-HBNPs developed by the team have a diameter of approximately 200 nm, with a drug loading efficiency exceeding 20% and a slow-release profile (releasing less than 15% of the drug over 96 hours). They also demonstrate excellent biocompatibility, with hemolysis rates below 5% at therapeutic doses. In in vitro experiments, fluorescently labeled HBNPs bound specifically to four different strains of K. pneumoniae , whereas control nanoparticles showed no specific binding.
In mice infected with K. pneumoniae , near-infrared labeled HBNPs accumulated exclusively in the lungs within 2 hours, with the intensity of the fluorescent signal directly proportional to the bacterial load in the infected tissue. Pharmacokinetic studies revealed that TIG-HBNPs extended TIG's half-life from 3.69 hours to 5.51 hours and maintained high drug concentrations in the lungs for up to 48 hours— a critical improvement over free TIG.
In a mouse model of K. pneumoniae -induced pneumonia, TIG-HBNPs outperformed free TIG significantly: they improved survival rates, reduced bacterial burden in the lungs, alleviated inflammation, and decreased macrophage infiltration. Importantly, no signs of toxicity were observed in healthy mice treated with the nanoparticles.
A key advantage of hemoglobin as a carrier is its status as an endogenous protein, which avoids the immunogenicity associated with synthetic carriers. Moreover, the TIG-HBNP platform is modular and can be adapted to target other pathogenic bacteria beyond K. pneumoniae . This work effectively transforms a systemically distributed antibiotic into a precision weapon against multidrug-resistant bacterial infections, opening new avenues for the treatment of drug-resistant pneumonia.
BMEF (BME Frontiers)
Experimental study
Animals
A Hemoglobin-Based Nanoparticle Delivery System Enhances the Pharmacokinetics and Efficacy of Tigecycline in Klebsiella pneumoniae Infections
30-Mar-2026