A hypoxia-activatable theranostic agent with intrinsic endoplasmic reticulum affinity and type-I photosensitivity?

Journal of Materials Chemistry B Pub Date: 2023-04-26 DOI: 10.1039/D3TB00328K

Abstract

A unique photosensitizer (PS), ERPS, with intrinsic endoplasmic reticulum (ER)-targeting ability and low oxygen-depletion type-I photosensitivity, is developed and used as a scaffold to construct an activatable theranostic agent for precise photodynamic therapy (PDT). The ER-targeted feature coupled with type-I photosensitivity endows ERPS with high phototoxicity toward tumor cells under both normoxic and hypoxic conditions. In addition, caging the phenol group of ERPS with a nitroreductase-sensitive triggering group provided a hypoxia-activatable PS (ERPSIm) that is encapsulated within a polymeric micelle to obtain a water-stable Im@NP nanoparticle for in vivo applications. After intravenous administration to 4T1 tumor-bearing BALB/c mice, Im@NP demonstrated highly efficient imaging-guided PDT ablation of implanted tumors. This is because the delivered ERPSIm cargos of Im@NP are specifically activated in the hypoxic microenvironment of solid tumor, and the activated ERPS molecules have efficient ER-targeted type-I photosensitivity.

Graphical abstract: A hypoxia-activatable theranostic agent with intrinsic endoplasmic reticulum affinity and type-I photosensitivity
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