New Assay Accurately Measures Whether Drugs Actually Reach the Cell Interior | Research

The takeaway

The CHAMP assay provides high-throughput, accurate measurement of cytosolic drug delivery, distinguishing truly internalized molecules from those stuck on membranes or in endosomes.

Cytosol vs stuck
CHAMP distinguishes drugs that reach the cytosol from those trapped on membranes or in endosomes

What the researchers found

The CHAMP assay (Chloroalkane HaloTag Azide-based Membrane Penetration) accurately reports cytosolic accumulation in high throughput, distinguishing true cytosolic delivery from membrane association or endosomal trapping.

Why it matters

Most biologics and peptide drugs fail because they can't reach intracellular targets. An accurate cytosolic delivery assay could dramatically improve drug development success rates.

How the study worked

Development and validation of the CHAMP assay for measuring cytosolic drug delivery using a minimally disruptive azide tag in mammalian cells.

What this study cannot tell us

Assay requires azide-tagged compounds — tag may alter some molecules' behavior. Validated in mammalian cell lines; tissue-specific penetration may differ.

How to read the evidence

Methods development paper — validates a new research tool rather than testing a specific therapeutic.

When this study was published

Published in 2026; addresses a long-standing gap in drug delivery assessment.

The bigger picture

This tool enables rational optimization of drug delivery systems for the growing field of intracellular therapeutics, including peptide drugs, PROTACs, and gene therapies.

Questions still open

Can the CHAMP assay be adapted for in vivo drug delivery assessment?
Does cytosolic accumulation measured by CHAMP correlate with therapeutic efficacy?

Common questions

Why is it hard to get drugs inside cells?

Cell membranes act as barriers that block most large molecules like peptides and biologics. Even when drugs cross the membrane, many get trapped in vesicles (endosomes) and never reach their targets in the cytosol.

What makes the CHAMP assay different?

Unlike existing tests that measure total cellular uptake, CHAMP specifically measures whether drug molecules reach the cytosol — the cell interior where most drug targets are located — giving a much more accurate picture of drug delivery.

Read the original research

A generalizable assay for intracellular accumulation to profile cytosolic drug delivery in mammalian cells.

Communications chemistry, 9(1), 94

View on PubMed ↗Publisher’s paper ↗

Citation

Bhandari, Sobika; Ongwae, George M; Dash, Rachita; Liu, Zichen; Chordia, Mahendra D; He, Yuchen; Pires, Marcos M. (2026). A generalizable assay for intracellular accumulation to profile cytosolic drug delivery in mammalian cells.. Communications chemistry, 9(1), 94. https://doi.org/10.1038/s42004-026-01898-8