# Recent advances in mitochondria-targeted porphyrin-based metal-organic frameworks for enhanced cancer therapy

## TL;DR

Researchers have developed porphyrin-based metal-organic frameworks that target mitochondria to improve cancer therapy by delivering reactive oxygen species and overcoming treatment resistance.

## Contribution

The paper introduces mitochondria-targeted porphyrin-MOFs that enable precise, multimodal cancer therapy through enhanced ROS delivery and organelle-specific targeting.

## Key findings

- Porphyrin-MOFs functionalized with mitochondria-targeting ligands improve photodynamic therapy by delivering ROS directly to mitochondria.
- These MOFs can be used in sonodynamic and radiodynamic therapies, enhancing oxidative damage and overcoming resistance mechanisms.
- The platforms support multimodal cancer treatment and have potential for intelligent, stimuli-responsive theranostic applications.

## Abstract

Porphyrin-based metal-organic frameworks (MOFs) offer exceptional advantages for cancer therapy, including high photosensitizer loading, tunable nanostructures, and suppression of porphyrin self-quenching. By functionalizing with mitochondria targeting ligands, these platforms deliver reactive oxygen species (ROS) precisely to mitochondria, the oxygen-rich and ROS-sensitive organelle, dramatically enhancing photodynamic therapy (PDT) efficacy. This design paradigm has been successfully extended to sonodynamic therapy (SDT) and radiotherapy/radiodynamic therapy (RT-RDT), where porphyrin-MOFs integrate additional functions such as glutathione depletion, CO/H2S gas release, or immune activation. Upon ultrasound or X-ray irradiation, these systems synergistically amplify mitochondrial oxidative damage, overcoming hypoxia, antioxidant defenses, and apoptosis resistance. The diversified applications (PDT, SDT and RDT) exemplifies a multimodal strategy that leverages the unique physicochemical properties of porphyrin-MOFs to achieve spatiotemporally controlled, organelle-specific therapy. Looking ahead, the development of intelligent, stimuli-responsive porphyrin-MOF nanoplatforms holds great promise for clinical translation, enabling integrated theranostics and personalized cancer treatment through precise mitochondrial targeting.