# Photo‐Empowered Macrophage‐Based Drug Delivery System Overcomes Motility Suppression and Significantly Enhances Deep Tumor Drug Delivery

## TL;DR

A new drug delivery system using light-activated macrophages improves drug delivery to deep tumors and fights drug resistance.

## Contribution

A novel photo-empowered macrophage-based system is developed to enhance drug delivery and overcome tumor hypoxia and resistance.

## Key findings

- The PEM system significantly improves drug delivery efficiency to deep tumor tissues.
- The system effectively eradicates hypoxic and drug-resistant tumor cells.
- Light-stimulated thylakoids enhance macrophage motility in the tumor microenvironment.

## Abstract

Recently, cell‐based drug delivery systems emerge as highly promising alternatives in the field of antitumor therapy. These systems are characterized by their excellent biocompatibility, robust drug‐loading capacity, and the ability to effectively traverse biological barriers. However, the immunosuppressive tumor microenvironment significantly weakens the motility of immune cells, which is crucial for efficient drug delivery. A novel photo‐empowered macrophage‐based (PEM) drug delivery system is successfully developed in this study. The system is modified with thylakoids extracted from spinach leaves. Upon stimulation with light of specific wavelengths, the thylakoids generate ATP through photochemical reactions, thereby significantly enhancing the motility of macrophages and effectively overcoming the limitations imposed by the tumor microenvironment. In this work, the PEM system is loaded with two antitumor drugs: doxorubicin (Dox) and tirapazamine (TPZ). The results demonstrate that the system not only significantly improves the delivery efficiency of drugs to deep tumor tissues but also greatly enhances antitumor therapeutic efficacy. Particularly after deep infiltration into tumor tissues, the PEM system efficiently eradicates hypoxic and drug‐resistant tumor cells, showcasing remarkable performance. This innovative PEM strategy provides a new approach for deep tumor drug delivery and addressing multidrug resistance, holding great promise for a significant breakthrough in antitumor therapy.

This study develops a photo‐empowered macrophage‐based (PEM) drug delivery system that provides a novel and effective solution for restoring cellular motility to enhance drug delivery and overcome hypoxia‐induced multidrug resistance. The construction of the PEM system fully exploits the unique biological properties of macrophages and the energy‐generating capabilities of thylakoids, drawing inspiration from the process of photosynthesis in plants.