Ultra-small Nano-assemblies as Tumor-targeted and Renal Clearable Theranostic Agent for Photodynamic Therapy.

It is a challenge to design photosensitizers to balance between the tumor-targeting enrichment for precise treatment and efficient clearance within a reasonable timescale for reducing side effects. Herein, we report an ultra-small nano-photosensitizer 1a with excellent tumor-specific accumulation and renal clearance. It was formed from the self-assembly of compound 1 bearing three TEG arms and two pyridinium groups in water. The positively charged surface with neutral TEG coating enables 1a to efficiently target the tumor, with the signal-to-background ratio reaching as high as 11.5 after tail intravenous injection. The ultra-small size of 1a with an average diameter of 5.6 nm allows its fast clearance through kidney. Self-assembly also endows 1a with an 18.2-fold enhancement of ROS generation rate compared to compound 1 in organic solution. Nano-PS 1a manifests an excellent PDT efficacy on tumor-bearing mouse models. This work provides a promising design strategy of photosensitizers with renal clearable and tumor-targeting ability. This article is protected by copyright. All rights reserved.