# Calixarene-Based Nanostructures for Delivering Coumarin 6 for Tumor-Cell Imaging and Photoinduced Toxicity

## TL;DR

This paper introduces a fluorescent nanosystem that targets and kills cancer cells using a calixarene-based carrier and Coumarin 6, showing potential for cancer imaging and treatment.

## Contribution

A novel calixarene-based nanosystem for targeted tumor imaging and photodynamic therapy using Coumarin 6 is developed.

## Key findings

- The nanosystem selectively targets cancer cells overexpressing the choline transporter.
- Visible-light irradiation activates Coumarin 6 to induce cancer cell death.
- The nanosystem shows excellent colloidal stability and fluorescence performance.

## Abstract

Fluorescence imaging
techniques are emerging as safer
and more
sensitive alternatives to radionuclide-based approaches for cancer
diagnosis. Entrapping fluorophores that also act as photosensitizers
within nanocarriers is an effective strategy to enhance their stability,
performance, and selective delivery to tumor tissues, enabling the
development of advanced nanosystems for cancer cell imaging and theranostic
applications. In this work, we report a fluorescent nanosystem obtained
by entrapping Coumarin 6 in biocompatible nanostructures formed through
the self-assembly of an amphiphilic calix[4]­arene derivative functionalized
with choline ligands for targeting tumor cells. The nanosystem was
characterized using diverse techniques, which confirmed nanoscale
organization, colloidal stability, excellent resistance to freeze-drying,
good fluorescence quantum yield, and visible-light-triggered photodynamic
activity, as evidenced by methylene blue photodegradation. Molecular
modeling simulations provided mechanistic insight into the host–guest
interactions governing Coumarin 6 stabilization in the nanocarrier.
The nanosystem selectively imaged breast carcinoma (MCF-7 and MDA-MB-231)
and hepatocarcinoma (Hep3B and SNU398) cells that overexpress the
choline transporter, while negligible uptake was observed in nonmalignant
human fibroblasts (HuDe cells). Intracellular fluorescence intensity
correlated with choline transporter expression levels, and the competitive
inhibition assay supported a transporter-mediated cellular uptake
mechanism. Upon biocompatible visible-light irradiation, the nanosystem
effectively induced cancer cell death through activation of the Coumarin
6 photosensitizer. The integration of targeted cancer cell imaging
and phototriggered cytotoxicity highlights this fluorescent nanosystem
as a promising photoresponsive nanotheranostic candidate.