Newsletter September: Evaluating drug selectivity and reducing toxicity

Welcome to the September edition of the AI for Live Cell Insights Newsletter, bringing you the latest live cell analyses powering drug discovery and cosmetics development. Each month, we will explore a new application of AI-based cellular analysis for label-free live cell imaging, with publication highlights and news from Nanolive. This month, we focus on drug selectivity, and how Nanolive’s technology increases biological relevance, while minimizing the damage from invasive imaging. Finally, we feature recent publications spanning immuno-oncology, mitochondria, nanomaterials, and cell death.

Evaluating drug selectivity with in vitro models

Drug selectivity is essential for maximizing therapeutic efficacy while minimizing toxicity to healthy cells, a key driver of clinical success. Measuring drug effects on target cells alone often overlooks off-target toxicity that can deprioritize promising candidates. Nanolive’s LIVE Cytotoxicity Assay recreates a more biologically relevant complexity using co-cultures, continuously quantifying cell responses, distinguishing direct from bystander effects, and identifying off-target toxicity to support the selection of the most effective, selective drug candidates with higher translational relevance. For example, live cell imaging can be used to characterize the timing of antibody-drug conjugate (ADC) effects, monitored separately in target and bystander cell populations, to shed light on the ADC bystander effect and mechanism of action.

Case study: Validating anti-cancer drug selectivity

This case study is available as a poster to download here:

Key takeaways

• On-target vs. off-target: Differentiate selective killing from unwanted toxicity.

• Mechanism insights: Detect apoptosis vs. necrosis in real-time.

• Scalable screening: Full 96-well plate, time-resolved readouts.

• More predictive outputs: Mixed-culture data with higher translational relevance.

A single fluorophore to power multiple readouts

Nanolive imaging reduces both bias and phototoxicity by replacing multiple stains and excitation channels with AI-powered image analysis to quantify cellular responses and cytotoxicity. Only a single fluorophore is then needed to distinguish between cell populations in co-culture. This assay can be applied to co-cultures of different cell types, or even morphologically-identical cells with different surface marker expression profiles, for example.

Discover more case studies utilizing Nanolive’s fluorescent quantification in our Drug Delivery Application Note.

Latest publication highlights with Nanolive imaging:

• Cell death: Sun, J., et al. (2025) ‘Delaying pyroptosis with an AI-screened gasdermin D pore blocker mitigates inflammatory response’, Nature Immunology https://doi.org/10.1038/s41590-025-02280-x

• Mitochondria in cancer: Hu, D.-W., et al. (2025) ‘SLC6A14 Drives Mitochondrial Fusion and Oxidative Phosphorylation to Promote Cancer Stemness and Early-Onset of Breast Cancer’, Advanced Science https://doi.org/10.1002/advs.202510811

• CAR-M therapy: Fu, J. et al. (2025) ‘A Bioactive Lipid Nanoparticle Integrating Arachidonic Acid Enables High-Efficiency mRNA Delivery and Potent CAR-Macrophage Engineering’ IJMS https://doi.org/10.3390/ijms26189199

• Nanomaterials: Courouble, J. et al. (2025) ‘Proton Beam-Induced Effects of Platinum Nanoparticles and Their Intracellular Localization’ Colloids and Surfaces B: Biointerfaces https://doi.org/10.1016/j.colsurfb.2025.115154

• Fungal infection: Nureki, O. et al. (2025) ‘Structural basis for tRNA-dependent sterol aminoacylation underlying cell membrane integrity’ Research Square https://doi.org/10.21203/rs.3.rs-7291846/v1

Find over 300 publications featuring Nanolive imaging here.

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