# Comparative assessment of antitumor effects between doxorubicin and mitochondria-targeted doxorubicin in combination with radiotherapy

## TL;DR

This study compares doxorubicin and a mitochondria-targeted version in combination with radiotherapy, showing improved tumor treatment effects.

## Contribution

The novel contribution is the development and evaluation of mitochondria-targeted doxorubicin (TPP-DOX) for enhanced antitumor efficacy with radiotherapy.

## Key findings

- TPP-DOX showed enhanced tumor cytotoxicity and improved cellular uptake compared to doxorubicin.
- TPP-DOX combined with radiotherapy significantly promoted tumor cell apoptosis and reduced mitochondrial membrane potential.
- In vivo experiments confirmed superior anti-tumor activity and safety profile of TPP-DOX with radiotherapy.

## Abstract

Triphenylphosphine (TPP) and Doxorubicin (DOX) were conjugated to obtain Triphenylphosphine-Doxorubicin (TPP-DOX), which was applied in tumor cells for enhancement of DOX in mitochondria targeting. The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.

TPP-DOX was synthesized using the carbodiimide method. In vitro experiments were conducted with 4T1 cells (mouse breast cancer cell line) to assess apoptosis induction, mitochondrial targeting, reactive oxygen species (ROS) production, and mitochondrial membrane potential. The research evaluates the effects of TPP-DOX, DOX, and their combinations with radiotherapy. A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.

TPP-DOX was successfully synthesized and scrupulously verified. In vitro experiments showed that compared to DOX, TPP-DOX exhibited enhanced tumor cytotoxicity, improved cellular uptake in 4T1 cells, and increased apoptosis induction. Combined with radiotherapy, TPP-DOX promoted mitochondrial ROS production, reduced mitochondrial membrane potential, and amplified its anti-tumor effect. In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity, promoted tumor tissue apoptosis, inhibited tumor angiogenesis, and showed a favorable in vivo safety profile.

The study confirmed that when combined with radiotherapy, TPP-DOX promoted tumor cell apoptosis, and effectively enhanced the anti-tumor effect. In sensitive cells, TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy. TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application. These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.