Newsletter May 2024: In vitro drug candidate profiling

Welcome to the first 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 are kicking off with live cell analysis for cytotoxic drug profiling.

Live cell imaging for drug candidate profiling 

Phenotypic data from live cell imaging can be used to measure changes at the cellular and organelle levels, and can indicate responses such as cellular stress before cell death is detectable. Monitoring phenotypic changes over time in label-free images is therefore a sensitive and non-invasive method for detecting drug effects and mechanism of action. 

To characterize and assess multiple drug candidates, the group of José Padrón at Universidad de La Laguna used Nanolive SA holotomographic imaging, combined with automated analysis and machine learning software in their recent publication ‘Early pharmacological profiling of isatin derivatives as potent and selective cytotoxic agents’. Live imaging was identified as a key tool for quantifying and characterizing drug-induced phenotypic changes in cells;  

“Continuous live cell imaging allows to analyze the potency of the compounds and their predominant mode of death, in addition to the kinetics of cell death.” 

Cellular dry mass, form factor, area and compactness were quantified automatically during the 15h imaging period using EVE Analytics (Nanolive), and the mechanism of cell death was identified as necrosis by Nanolive’s LIVE Cell Death Assay (now the LIVE Cytotoxicity Assay) which uses machine learning to differentiate between living, apoptotic, and necrotic cells.  

To read the full paper Early pharmacological profiling of isatin derivatives as potent and selective cytotoxic agents, Puerta et al. (2024) click here.

Author testimonial

The Padron lab has been pioneering use of Nanolive’s AI technology since 2021, and provided the following testimonial for the LIVE Cell Death Assay (now the LIVE Cytotoxicity Assay): 

CX-A with 96-well plate

Holotomography and automated analysis

Nanolive’s label-free holotomographic technology makes it possible to image cells for long periods of time, at high resolution. The quantity and complexity of the images generated allows visualization of biological processes in unprecedented detail from the population to subcellular level. EVE Analytics forms the backbone of Nanolive’s digital assays for phenotypic analysis, providing a simple tool to segment and measure every cell automatically.  

To read the eBook for more details about holotomography, click here.

Cell segmentations carried out from refractive index
Example cell segmentations carried out from refractive index (RI) holotomographic images.

Monitoring cell health and stress in timelapse images

The LIVE Cytotoxicity Assay (previously the LIVE Cell Death Assay) can be used for label-free monitoring of phenotypic responses of cells, using morphological markers such as cell area, or Nanolive’s unique metric, the Health Cell Index. As well as cell death monitoring, this digital assay enables the detection of cell stress and stress-induced morphological changes to aid detection of drug candidates with harmful effects that cannot be detected by standard cytotoxicity assays. 

To learn how cell stress can be monitored using phenotypic data, and how anastasis (reversible apoptosis) can be detected, check out the case studies in our application note here.

CX-A with 96-well plate

Change in pre-adipocyte morphology during heatshock and imaging timelapse. Cells are digitally colored green (living) to brown (dead) by the LIVE Cytotoxicity Assay.

Latest publication highlights with Nanolive imaging:
  • Nanomaterials: Depciuch, J. et al. (2024) ‘Modeling Absorption Dynamics of Differently Shaped Gold Glioblastoma and Colon Cells Based on Refractive Index Distribution in Holotomographic Imaging’, Small, https://doi.org/10.1002/smll.202400778  
  • Immunooncology: Wang, W. et al. (2024) ‘Biological impact and therapeutic potential of a novel camptothecin derivative (FLQY2) in pancreatic cancer through inactivation of the PDK1/AKT/mTOR pathway’, Bioorganic Chemistry, https://doi.org/10.1016/j.bioorg.2024.107436  
  • Parasitology: Ross, R. et al. (2024) ‘Human dendritic cell interactions with the zoonotic parasite Cryptosporidium parvum result in activation and maturation’, Frontiers in Immunology, https://doi.org/10.3389/fimmu.2024.1388366  
  • Cellular metabolism: Lamela, F. et al. (2024) ‘Differential effects of coverslip-induced hypoxia and cobalt chloride mimetic hypoxia on cellular stress, metabolism, and nuclear structure’, Tissue & Cell,  https://doi.org/10.1016/j.tice.2024.102408 
  • Immunology: Yu, F. et al. (2024) Loss of the TRPM4 channel in humans causes immune dysregulation with defective monocyte migration, Journal of Allergy and Clinical Immunology, https://doi.org/10.1016/j.jaci.2024.02.026  
  • CAR-T engineering: Valentić, B. et al. (2024), The Glucose Transporter 5 Enhances CAR-T Cell Metabolic Function and Anti-tumour Durability, Research Square, https://doi.org/10.21203/rs.3.rs-4342820/v1  

Find over 250 publications featuring Nanolive imaging here

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2023 scientific publications roundup

2023 scientific publications roundup

2023 has been a record year for clients using the Nanolive system in their scientific publications. The number of peer-reviewed publications has continued to increase, and there has been a real growth in groups publishing pre-prints to give a preview of their work....

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