Self-Assembled Squalenoylated Penicillin Bioconjugates: An Original Approach for the Treatment of Intracellular Infections
Abstract
We describe here new nanoparticles based on the bioconjugation of penicillin G to squalene in order to overcome severe intracellular infections by pathogen bacteria whose mechanism of resistance arises from the poor intracellular diffusion of several antibiotics. Two different squalene-penicillin G conjugates were synthesized (pH-sensitive and pH-insensitive), and their self-assembly as nanoparticles was investigated through morphology and stability studies. These nanoparticles had a size of 140 ± 10 nm (polydispersity index of 0.1) and a negative charge, and they did not display any supramolecular organization. Furthermore, they were found stable in water and in different culture medium. The cellular uptake and localization of these fluorescently labeled nanoparticles were explored on the macrophage cell line J774 by flow cytometry and confocal microscopy analysis. The squalenoylated nanoparticles were found to be cell internalized through clathrin-dependent and -independent endocytic pathways. Moreover, they induced an improved intracellular antibacterial activity on the facultative intracellular pathogen S. aureus, compared with free penicillin G, despite the absence of co-localization between the bacteria and the nanoparticles in the cells. This study suggests that the bioconjugation of an antibiotic to a squalene template could be a valuable approach for overcoming the antibiotic resistance due to intracellular bacterial infections.
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Nanoparticles formed from penicillin G-squalene conjugate were rapidly taken up by cells and released drug in the endolysosomes, resulting in improved activity over the free drug.
“Nanoparticles formed from this conjugate were rapidly taken up by cells and released drug in the endolysosomes. This resulted in improved activity over the free drug.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [67]
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- Authors
- Sémiramoth, N., Meo, C. D., Zouhiri, F., Saïd-Hassane, F., Valetti, S., Gorges, R., Nicolas, V., Poupaert, J. H., Chollet-Martin, S., Desmaële, D., Gref, R., & Couvreur, P.
- Affiliations
- Université Paris-Sud (FR)
- Faculty of Pharmacy, UMR CNRS 8612, University of Paris-Sud XI, 5 Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France
- UCLouvain (BE)
- Faculty of Pharmacy, INSERM UMRS 996, University of Paris-Sud XI, 5 Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France
- Corresponding author
- Couvreur, Patrick
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-04-19
- Volume
- 6
- Issue
- 5
- Pages
- 3820-3831
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2057474764
- Cited by
- 133
- References
- 50
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 7 · 2023: 7 · 2022: 10 · 2021: 8 · 2020: 14 · 2019: 16 · 2018: 10 · 2017: 10 · 2016: 8 · 2015: 12 · 2014: 17 · 2013: 8 · 2012: 1
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Keywords
- nanoparticle self-assembly, bioconjugation, intracellular infection, antibiotic resistance, Staphylococcus aureus, pH-responsive nanoparticles, cellular uptake, endocytosis, clathrin-mediated endocytosis, macrophages, intracellular antibacterial activity, nanoparticle stability
- MeSH terms
- Bacterial Infections, Humans, Microbial Sensitivity Tests, Penicillins, Squalene, Microscopy, Electron, Transmission
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