image: In vivo distribution and targeting effect on K. pneumoniae of HBNPs/BSANPs. (A) Schematic diagram of the experimental procedure. (B and C) Live fluorescence images and fluorescence intensities of K. pneumoniae mice 0 to 8 h after injection of indocyanine green (ICG)–HBNP nanoparticles. (D and E) Live fluorescence images and fluorescence intensities of K. pneumoniae mice and normal mice 0 to 4 h after injection of PBS, ICG, ICG–HBNP, and ICG–BSANP nanoparticles. (F) Fluorescence images of major organs of K. pneumoniae mice and normal mice 4 h after injection of PBS, ICG, ICG–HBNP, and ICG–BSANP nanoparticles. (G and H) Fluorescence images and fluorescence intensities of the lungs of K. pneumoniae mice and normal mice 4 h after injection of ICG, ICG–HBNP, and ICG–BSANP nanoparticles. MFI, mean fluorescence intensity; ns, not significant.
Credit: Luo Lei Lab @ SWU-CPS.
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.
Journal
BMEF (BME Frontiers)
Method of Research
Experimental study
Subject of Research
Animals
Article Title
A Hemoglobin-Based Nanoparticle Delivery System Enhances the Pharmacokinetics and Efficacy of Tigecycline in Klebsiella pneumoniae Infections
Article Publication Date
30-Mar-2026