# Alkali Lignin-Based Biopolymer Formulations for Electro-Assisted Drug Delivery of Natural Antioxidants in Breast Cancer Cells—A Preliminary Study

**Authors:** Severina Semkova, Radina Deneva, Georgi Antov, Donika Ivanova, Biliana Nikolova

PMC · DOI: 10.3390/ijms26157481 · 2025-08-02

## TL;DR

This study explores using alkali lignin-based biopolymers to deliver natural antioxidants like Quercetin to breast cancer cells using an electro-assisted method.

## Contribution

The novelty lies in using alkali lignin-based formulations for electro-assisted delivery of natural antioxidants to breast cancer cells.

## Key findings

- Lignin@Formulations showed slight sensitivity in cancer cells compared to healthy cells.
- Electric pulses enhanced the effect of the formulations on cancer cells.
- Quercetin-loaded L@F was tested on a highly metastatic breast cancer cell line.

## Abstract

Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the possibility of their use for novel applications in various industrial branches, including biomedicine. In this regard, the safety, efficiency, advantages and limitations of lignin compounds for in vitro/in vivo applications remain poorly studied and described. This study was carried out to investigate the possibility of using newly synthesized, alkali lignin-based micro-/nano-biopolymer formulations (Lignin@Formulations/L@F) as carriers for substances with antioxidant and/or anticancer effectiveness. Moreover, we tried to assess the opportunity for using an electro-assisted approach for achieving improved intracellular internalization. An investigation was conducted on an in vitro panel of breast cell lines, namely two breast cancer lines with different metastatic potentials and one non-tumorigenic line as a control. The characterization of all tested formulations was performed via DLS (dynamic light scattering) analysis. We developed an improved separation procedure via size/charge unification for all types of Lignin@Formulations. Moreover, in vitro applications were investigated. The results demonstrate that compared to healthy breast cells, both tested cancer lines exhibited slight sensitivity after treatment with different formulations (empty or loaded with antioxidant substances). This effect was also enhanced after applying electric pulses. L@F loaded with Quercetin was also explored only on the highly metastatic cancer cell line as a model for the breast cancer type most aggressive and non-responsive to traditional treatments. All obtained data suggest that the tested formulations have potential as carriers for the electro-assisted delivery of natural antioxidants such as Quercetin.

## Linked entities

- **Chemicals:** Quercetin (PubChem CID 5280343)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Diseases:** Breast Cancer (MESH:D001943), tumorigenic (MESH:D002471), cancer (MESH:D009369)
- **Chemicals:** Quercetin (MESH:D011794), lignin (MESH:D008031), Alkali Lignin (-)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12347630/full.md

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Source: https://tomesphere.com/paper/PMC12347630