Rational Design of Self-Reporting Photosensitizers for Cell Membrane-Targeted Photodynamic Therapy

Abstract

Organelle-targeted photosensitizers (PSs) have demonstrated enhanced phototherapeutic effect by specifically destroying subcellular organelle. As a critical cellular organelle, the cell membrane plays crucial roles in maintaining cell integrity and regulating cellular communications. To date, a variety of membrane-targeted PSs have been developed and shown exceptional therapeutic effects. However, functional PSs that can achieve membrane-targeted photodynamic therapy (PDT) and real-time monitor the therapeutic process have rarely been reported. In particular, the development of self-reporting PS with near-infrared (NIR) absorption is highly desirable but remains a challenge. Herein, we presented two molecular rotor-based self-reporting PSs. One of the PSs, MRMP-2, possesses NIR absorption property, making it a promising candidate for clinical applications. These PSs could not only enable membrane-targeted PDT but also demonstrate selective fluorescence response toward viscosity. In this regard, the fluorescence variation of these PSs could be utilized to indicate the disruption of membrane structure during PDT process. By leveraging the feedback of the fluorescence signal, we could make intuitive judgement about the phototherapeutic results. As a result, these two PSs possess significant potential in the field of imaging-guided PDT.

Cancer-cell-specific Self-Reporting Photosensitizer for Precise Identification and Ablation of Cancer Cells

“…As the most important agent in PDT for cancer treatment, fluorescent PSs with cancer-cell targeting ability could be activated under light irradiation to harvest toxic reactive oxygen species (ROS) in cancer cells selectively, resulting in the degradation of cancerous masses. − In present, the cancer-cell-targeted fluorescent PSs are mainly designed based on a tumor-specific microenvironment, which are usually modified with activable groups. For example, Zhou et al reported an enzyme-activated PS, APN-CyI, which could target the Aminopeptidase N that overexpressed on the surface of tumor cells .…”