# In Situ Lipid Interactions of an Anticancer Metal Complex

**Authors:** Edward C. Lant, Archana C. Jadhav, Annabel Sumeray, Gustavo F. Trindade, Luca Craciunescu, Andrew W. Prentice, Juliusz A. Wolny, Jaspreet S. Grewal, Robert Dallmann, Guy J. Clarkson, Ann M. Dixon, Volker Schünemann, Ian S. Gilmore, Martin J. Paterson, Maria Harkiolaki, Peter J. Sadler

PMC · DOI: 10.1021/acs.inorgchem.6c00104 · Inorganic Chemistry · 2026-03-13

## TL;DR

A new anticancer metal complex interacts with cell lipids, showing strong effects on membranes and lipid structures in cancer cells.

## Contribution

The discovery of unexpected lipid targeting and supramolecular interactions of a Rh(III) anticancer complex.

## Key findings

- The Rh(III) complex accumulates in plasma membranes and shows intense luminescence in cancer cells.
- The complex induces lipid droplet architecture remodeling and interacts strongly with glycerophosphorylcholine lipids.
- Multimodal imaging and DFT modeling reveal deep penetration into lipid-rich tissues.

## Abstract

An integrated multimodal imaging workflow of cryogenic
super-resolution
fluorescence microscopy and soft X-ray tomography, Orbitrap secondary
ion mass spectrometry, and inductively coupled plasma-mass spectrometry
has revealed the unexpected targeting of a half-sandwich cyclopentadienyl
Rh­(III) phenylazopyridine anticancer complex to cellular lipid membranes
and lipid droplets. The complex accumulates in plasma membranes with
a surprisingly intense switch-on luminescence in living cancer cells,
drives remodeling of lipid droplet architecture, and penetrates deeply
into lipid-rich tissue environments. DFT modeling shows strong supramolecular
interactions between the complex and glycer­ophos­phoryl­choline
lipids.

## Linked entities

- **Chemicals:** glycerophosphorylcholine (PubChem CID 657272)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Diseases:** cytotoxic (MESH:D064420), lung cancer (MESH:D008175), cryoSIM (MESH:D020914), ICPMS (MESH:C536030), cancer (MESH:D009369)
- **Chemicals:** dilauroylphosphatidylcholine (MESH:C015153), Platinum (MESH:D010984), Cl (MESH:D002713), triacyl glycerols (MESH:D014280), cisplatin (MESH:D002945), Lipid (MESH:D008055), DOPC (MESH:C017251), gold (MESH:D006046), pyridine (MESH:C023666), Si6 (-), C4 (MESH:C058899), Phenazopyridine (MESH:D010621), carbon (MESH:D002244), Rh (MESH:D012238), choline (MESH:D002794), Metal (MESH:D008670), LysoTracker (MESH:C493330), azo dye (MESH:D001391), N (MESH:D009584), Ar (MESH:D001128), PO (MESH:D011059), phosphate (MESH:D010710), cholesteryl esters (MESH:D002788), glycerophosphorylcholine (MESH:D005997), Phospholipids (MESH:D010743), silicon (MESH:D012825)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** A549 lung adenocarcinoma — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_WN45), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC13040523/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13040523/full.md

## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC13040523/full.md

---
Source: https://tomesphere.com/paper/PMC13040523