# Near Infrared‐light responsive chlorin e6 pro‐drug micellar photodynamic therapy for oral cancer

## TL;DR

This paper introduces a new light-responsive nanomedicine that improves photodynamic therapy for oral cancer by targeting tumors and reducing side effects.

## Contribution

A novel 2-nitrobenzyl-linked micellar system enables controlled release of chlorin e6 under near-infrared light for targeted photodynamic therapy.

## Key findings

- The mPNCe6 micelles showed rapid and controlled release of Ce6 upon near-infrared light exposure.
- The formulation significantly reduced tumor growth and lung metastasis in mice.
- Ce6 conjugation improved cellular uptake and ROS generation, enhancing photodynamic efficacy.

## Abstract

A major concern of conventional photodynamic therapy is its non‐specific toxicity due to off‐site drug accumulation. Micelles tend to localize the drug to the tumor site. However, rapid drug release at high concentrations from the micelles to kill the cancer cells remains a formidable task. In this manuscript, we have introduced the 2‐nitrobenzyl (2NB)‐moiety as the linker between mPEG and the photosensitizer, chlorin e6 (Ce6), to prepare the conjugate, mPEG(2‐nitrobenzyl)Ce6. We envision that 2NB as a linker between hydrophobic, Ce6, and hydrophilic mPEG would be more effective in releasing Ce6 by disassembling PEGylated 2‐nitrobenzyl chlorin e6 (mPNCe6) Ms. Characterization through Fourier transform infrared spectroscopy and 1H, 13C nuclear magnetic resonance spectra validated the successful synthesis of the conjugate. By conjugating Ce6 into the hydrophobic core of the micelles, exposure to near‐infrared light significantly hastened the dissociation of the micelles, facilitating a controlled and rapid release of Ce6's hydrophobic components within the micelles. A cellular uptake study was performed, showing that Ce6 conjugation has improved the uptake of Ce6. The cell viability assay revealed that the formulation had shown concentration‐dependent cytotoxicity upon laser irradiation. mPNCe6 group with laser irradiation has generated abundant reactive oxygen species (ROS) inside cells and exhibited green solid fluorescence, indicating the efficient delivery of Ce6 by mPNCe6 micelles and its excellent ROS generation ability inside cells upon laser irradiation. Further, in vivo studies on MOC2 tumor‐bearing mice demonstrate reduced tumor growth, lung metastasis, and drug accumulation in the tumor region. The developed nanomedicine could be a potential treatment strategy for oral cancer, minimizing the occurrence of lung metastasis.