Shamsuddeen Ma'aruf Poster 2024

Mr Shamsuddeen Ma'aruf

Stellenbosch University, South Africa

Anti-mycobacterial Efficacy of Curdlan-Functionalized Nanoparticles and their Influence on Macrophage Phenotype in vitro

Poster Abstract

The global burden of tuberculosis (TB) persists, necessitating innovative therapeutic strategies due to treatment failures and the emergence of drug-resistant strains. Bacterial persisters contribute to treatment challenges, prompting the exploration of new approaches. This study investigates the potential of lipid-polymer hybrid nanoparticles (LPN), specifically Curdlan (CN)-functionalized NPs, to enhance intracellular killing of Mycobacterium tuberculosis.

The research employs in vitro assays using bone marrow-derived macrophages (BMDMs) and an attenuated M. tuberculosis strain with luminescent monitoring. CN-functionalized NPs exhibit robust anti-mycobacterial efficacy, aligning with prior in vivo findings. Notably, real-time luminescence monitoring validates their potency against M. tuberculosis. Expanding the investigation to macrophage responses, the study examines the impact of NPs on macrophage phenotype and function using techniques such as multiplex cytokine assay and transcriptomic analysis. Results unveil an affinity between CN-functionalized NPs and macrophages, influencing their immunologic activity. These NPs stimulate pro-inflammatory cytokines (IFN-ɣ, IL-1β, IL-12p70, IL-18, IL-2, IL-5, TNF-α, and IL-6), indicating a shift towards the M1 phenotype, known for effective M. tuberculosis control. This comprehensive analysis underscores the consistency of M. tuberculosis strain replication, affirming its suitability for TB research. Additionally, CN-functionalized NPs emerge as promising agents, impacting macrophage responses and enhancing M1 marker expression. The study contributes vital insights into the intricate interplay between nanoparticles and macrophages during TB treatment, addressing a knowledge gap.

While emphasizing the potential of CN-functionalized nanoparticles in TB therapy, the study underscores the need for further investigations. Concentration-dependent anti-mycobacterial activity and transcriptomic responses warrant exploration. In conclusion, this research expands our understanding of TB treatment dynamics and underscores the evolving role of nanoparticles, signalling avenues for targeted therapeutic interventions in tuberculosis. Further research is imperative to harness the full potential of nanoparticle-mediated approaches in TB treatment.