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Alkyne-Tagged PLGA Allows Direct Visualization of Nanoparticles In Vitro and Ex Vivo by Stimulated Raman Scattering Microscopy.

ABSTRACT: Polymeric nanoparticles (NPs) are attractive candidates for the controlled and targeted delivery of therapeutics in vitro and in vivo. However, detailed understanding of the uptake, location, and ultimate cellular fate of the NPs is necessary to satisfy safety concerns, which is difficult because of the nanoscale size of these carriers. In this work, we show how small chemical labels can be appended to poly(lactic acid-co-glycolic acid) (PLGA) to synthesize NPs that can then be imaged by stimulated Raman scattering microscopy, a vibrational imaging technique that can elucidate bond-specific information in biological environments, such as the identification of alkyne signatures in modified PLGA terpolymers. We show that both deuterium and alkyne labeled NPs can be imaged within primary rat microglia, and the alkyne NPs can also be imaged in ex vivo cortical mouse brain tissue. Immunohistochemical analysis confirms that the NPs localize in microglia in the mouse brain tissue, demonstrating that these NPs have the potential to deliver therapeutics selectively to microglia.

SUBMITTER: Vanden-Hehir S

PROVIDER: S-EPMC6794644 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Alkyne-Tagged PLGA Allows Direct Visualization of Nanoparticles In Vitro and Ex Vivo by Stimulated Raman Scattering Microscopy.

Vanden-Hehir Sally S Cairns Stefan A SA Lee Martin M Zoupi Lida L Shaver Michael P MP Brunton Valerie G VG Williams Anna A Hulme Alison N AN

Biomacromolecules 20190829 10

Polymeric nanoparticles (NPs) are attractive candidates for the controlled and targeted delivery of therapeutics in vitro and in vivo. However, detailed understanding of the uptake, location, and ultimate cellular fate of the NPs is necessary to satisfy safety concerns, which is difficult because of the nanoscale size of these carriers. In this work, we show how small chemical labels can be appended to poly(lactic acid-<i>co</i>-glycolic acid) (PLGA) to synthesize NPs that can then be imaged by ...[more]

PMID: 31408325

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Project description:Antibiotics resistance developed by biofilms has posed a clinical challenge in the effective treatment of bacterial infections. However, the resistance mechanisms have not been well understood due to a lack of suitable tools for dynamic observation of the interplay between antibiotics and biofilm. In this work, with the use of rapid hyperspectral stimulated Raman scattering microscopy associated with an aryl-alkyne-based Raman tag synthesized, we investigate dynamic interactions between vancomycin and Staphylococcus aureus (S. aureus) biofilm to gain new insights into the resistance mechanisms of the biofilm. Methods: We utilize spectral focusing hyperspectral stimulated Raman scattering microscopy ensued with multivariate curve resolution analysis to spectrally decompose S. aureus biofilm into its major components (i.e., bacteria and extracellular polymeric substances). Concurrently, vancomycin is conjugated with aryl-alkyne Raman tag (Raman peak at 2218 cm-1) for in vivo tracking of its uptake into biofilm without tissue interference. Results: We find that vancomycin penetration is a non-uniform diffusion process with penetration depths limited by the preferential affinity to the cell clusters. Semi-quantitative analysis shows that the majority of vancomycin binds to the bacteria, achieving intracellular concentrations of up to 4- to 10- fold higher than the administered dosage. The diffusion constant of ~3.16 µm2/min based on the diffusion and antibiotic binding equations is obtained that well accounts for the antibiotic penetration into the biofilm. SRS longitudinal monitoring of antibiotic effect on the growth of biofilms shows that the antibiotics can eradicate the upper layer of the biofilm exposed to sufficient dosages, while the lower layer of the biofilm at a sub-inhibitory dose remains viable, eventually re-growing to significant bio-volume. Conclusion: The Raman-tagged hyperspectral SRS microscopy developed is a powerful imaging tool for dynamic monitoring of inhibitory effects of antibiotics on the growing biofilm in vivo, which would facilitate the formulation of new antibiotics for more effective treatments of bacterial infections in near future.

Dataset Information

Alkyne-Tagged PLGA Allows Direct Visualization of Nanoparticles In Vitro and Ex Vivo by Stimulated Raman Scattering Microscopy.

Publications

Alkyne-Tagged PLGA Allows Direct Visualization of Nanoparticles In Vitro and Ex Vivo by Stimulated Raman Scattering Microscopy.

Similar Datasets

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