De novo design of a dual-emissive self-reporting photosensitizer with high membrane permeability via chain-engineering strategy

Abstract

Photodynamics therapy (PDT) is an important and advantageous method for the selective ablation of tumor cells. However, the reported PDT sensitizers remain two critical problems: firstly, dual-emissive self-reporting photosensitizers have not been reported for the monitoring and control of light irradiation; secondly, high loading concentration (usually at micromolar concentration) of the photosensitizers was used. Herein, we have designed a dual-emissive self-reporting photosensitizer with low loading concentration (200 nM) to resolve the two knots. 4-Aminostyryl-methyl-benzothiazolium was selected as the photosensitizer, which can generate 1O2 upon light irradiation, and displayed red-shifted absorption when binding to RNA. Meanwhile different chains were modified to optimize the RNA affinity and membrane permeability concurrently. Finally, the photosensitizer with C4 chain (NPT-4) was screened out. NPT-4 targeted mitochondria in living cells to give green and red fluorescence with the excitation of 488 nm and 561 nm, respectively. During cell death, NPT-4 translocated into RNA to give dramatically decreased green emission and unchanged red fluorescence. Therefore, NPT-4 simultaneously induced and reported the damages of tumor cells upon light irradiation in dual-emissive manner. Further, NPT-4 exhibited high membrane permeability, and 200 nM NPT-4 can brightly light up the cells and efficiently induce cell damages with light irradiation. Accordingly, NPT-4 is expected to be an important self-reporting photosensitizer for PDT and relative studies.