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Published on: February 5, 2019
Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial
Xucheng Hou1, Xinfu Zhang1,2, Weiyu Zhao1
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Abstract:
Sepsis, a condition caused by severe infections, affects more than 30 million people worldwide every year and remains the leading cause of death in hospitals1,2. Moreover, antimicrobial resistance has become an additional challenge in the treatment of sepsis3, and thus, alternative therapeutic approaches are urgently needed2,3. Here, we show that adoptive transfer of macrophages containing antimicrobial peptides linked to cathepsin B in the lysosomes (MACs) can be applied for the treatment of multidrug-resistant bacteria-induced sepsis in mice with immunosuppression. The MACs are constructed by transfection of vitamin C lipid nanoparticles that deliver antimicrobial peptide and cathepsin B (AMP-CatB) mRNA. The vitamin C lipid nanoparticles allow the specific accumulation of AMP-CatB in macrophage lysosomes, which is the key location for bactericidal activities. Our results demonstrate that adoptive MAC transfer leads to the elimination of multidrug-resistant bacteria, including Staphylococcus aureus and Escherichia coli, leading to the complete recovery of immunocompromised septic mice. Our work provides an alternative strategy for overcoming multidrug-resistant bacteria-induced sepsis and opens up possibilities for the development of nanoparticle-enabled cell therapy for infectious diseases.
Insights
New cell therapy using macrophages loaded with antimicrobial peptides effectively treats multidrug-resistant sepsis in mice. This nanoparticle-based approach offers a promising alternative for severe infections, especially in immunocompromised patients.
Area of Science:
- Immunology
- Nanomedicine
- Infectious Diseases
Background:
- Sepsis affects over 30 million globally, causing significant mortality.
- Antimicrobial resistance complicates sepsis treatment, necessitating novel therapies.
- Current treatments face challenges, especially with multidrug-resistant pathogens.
Purpose of the Study:
- To investigate nanoparticle-enabled macrophage therapy for multidrug-resistant sepsis.
- To evaluate the efficacy of macrophages engineered with antimicrobial peptides and cathepsin B (MACs).
- To assess MACs in an immunosuppressed mouse model of sepsis.
Main Methods:
- Engineered macrophages (MACs) were created using vitamin C lipid nanoparticles delivering antimicrobial peptide and cathepsin B (AMP-CatB) mRNA.
- Nanoparticles facilitated targeted accumulation of AMP-CatB within macrophage lysosomes.
- Adoptive transfer of MACs was performed in immunosuppressed mice with multidrug-resistant bacterial infections.
Main Results:
- MACs demonstrated efficient elimination of multidrug-resistant bacteria, including Staphylococcus aureus and Escherichia coli.
- Adoptive MAC transfer led to complete recovery in immunocompromised septic mice.
- The targeted delivery of AMP-CatB to lysosomes enhanced bactericidal activity.
Conclusions:
- Nanoparticle-mediated macrophage therapy presents a viable strategy against multidrug-resistant bacterial sepsis.
- This approach offers a novel therapeutic avenue for infectious diseases, particularly in challenging clinical scenarios.
- Further development of nanoparticle-enabled cell therapies holds promise for combating resistant infections.
