# Endoperoxide delivered singlet oxygen: the future of PDT, without light or oxygen

## TL;DR

A new cancer treatment uses chemically generated singlet oxygen to target tumors without needing light or oxygen, showing strong tumor suppression and no toxicity.

## Contribution

A novel therapeutic approach using endoperoxides to deliver singlet oxygen directly to tumors, bypassing limitations of traditional photodynamic therapy.

## Key findings

- Pyridone-endoperoxides with mitochondria-targeting moieties significantly suppressed tumors in mouse models.
- Endoperoxides showed no systemic or organ-level toxicity in tested models.
- Mitochondria targeting was confirmed as crucial for the effectiveness of the endoperoxide compounds.

## Abstract

Chemically generated singlet oxygen via cycloreversion reaction of aromatic endoperoxides is poised to evolve into a highly promising therapeutic protocol. Singlet oxygen can also be produced endogenically, with a short half-life especially in biological media, and it acts locally, only when a threshold value is exceeded. Conserving the essence of photodynamic therapy, which is the delivery of singlet oxygen to tumors, two limiting issues of light penetration and low tumor oxygenation can be circumvented simultaneously by endoperoxide-delivered singlet oxygen. The endoperoxides are also amenable to derivatization for more specific targeting as well. In this work, pyridone-endoperoxides with mitochondria targeting triphenylphosphonium moieties were shown to target tumors and result in significant tumor suppression. The series of endoperoxides tested also confirms the importance of mitochondria targeting. In mouse tumor models, these compounds show no signs of systemic or organ level toxicity.

Chemically generated singlet oxygen via cycloreversion reaction of aromatic endoperoxides is poised to evolve into a highly promising therapeutic protocol.