Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis
Open accessAbstract
Sepsis, a condition caused by severe infections, affects more than 30 million people worldwide every year and remains the leading cause of death in hospitals 1,2. Moreover, antimicrobial resistance has become an additional challenge in the treatment of sepsis 3, and thus, alternative therapeutic approaches are urgently needed 2,3. 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.
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Traditional antibacterial drugs are prone to become drug resistant due to their low efficiency and lack of targeting.
“However, traditional antibacterial drugs are prone to become drug resistant due to their low efficiency and lack of targeting.39,40”
From Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach (2022) · cites this paper as [40]
The Abstract (page unavailable) describes antimicrobial resistance as a challenge in treating sepsis and says persistent infections indicate a paucity of effective antimicrobial agents. It does not say that traditional antibacterial drugs cause resistance because of low efficiency or lack of targeting; the targeting it describes concerns the proposed nanoparticle therapy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAdoptive transfer of macrophages engineered by delivering mRNA that encodes an antimicrobial peptide considerably reduced bacterial burden and increased survival in mice with multidrug-resistant bacterial sepsis.
“Adoptive transfer of macrophages engineered by delivering mRNA that encodes an antimicrobial peptide considerably reduced bacterial burden and increased survival in mice with multidrug-resistant bacterial sepsis136.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [136]
A vitamin C-derived lipid nanoparticle allows mRNA delivery into primary macrophages.
“For example, a vitamin C-derived lipid nanoparticle allows mRNA delivery into primary macrophages136.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [136]
Lipid nanoparticle-mRNA formulations have been applied to produce therapeutic proteins or antibodies, to edit virus genomes and to engineer immune cells.
“In addition, lipid nanoparticle–mRNA formulations have been applied to produce therapeutic proteins or antibodies39,75,145,146, to edit virus genomes105 and to engineer immune cells136.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [136]
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References 29 · Cited by 290
- Authors
- Hou, X., Zhang, X., Zhao, W., Zeng, C., Deng, B., McComb, D. W., Du, S., Zhang, C., Li, W., & Dong, Y.
- Affiliations
- The Ohio State University (US)
- Dalian University of Technology (CN)
- Corresponding author
- Dong, Yizhou
- ORCID
- Venue
- Nature Nanotechnology
- Published
- 2020-01-02
- Volume
- 15
- Issue
- 1
- Pages
- 41-46
- ISSN
- 1748-3387 (ISSN-L)
- 1748-3395
- PMC
- PMC7181370
- OpenAlex
- W2998275193
- Cited by
- 290
- References
- 29
- Citations by year
- 2026: 38 · 2025: 49 · 2024: 54 · 2023: 54 · 2022: 40 · 2021: 38 · 2020: 17
- FWCI
- 12.08
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-04-28)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R35GM119679)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- sepsis, multidrug-resistant bacteria, adoptive macrophage transfer, antimicrobial peptides, cathepsin B, lysosomal delivery, mRNA delivery, Staphylococcus aureus, Escherichia coli, immunodeficient mice, antimicrobial resistance
- MeSH terms
- RAW 264.7 Cells, Animals, Anti-Bacterial Agents, Ascorbic Acid, Cathepsin B, Drug Carriers, Lipids, Liposomes, Macrophages, Mice, Inbred C57BL, RNA, Messenger, Vitamins, Sepsis, Adoptive Transfer, Antimicrobial Cationic Peptides, Drug Resistance, Multiple, Bacterial, Mice, Nanoparticles
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