Responsive Peptide Nanofibers with Theranostic and Prognostic Capacity

Dr. Bingbing Sun, Dr. Xiaoping Guo, Mei Feng, Shoupeng Cao, Haowen Yang, Dr. Hanglong Wu, Marleen H. M. E. van Stevendaal, Roy A. J. F. Oerlemans, Jinning Liang, Prof. Yiqiang Ouyang, Prof. Jan C. M. van Hest

Published: 2022

Graphical Abstract

A PEGylated porphyrin-peptide (PHHPEG6) building block self-assembled into nanofibers (NFs), which formed aggregates in the acidic tumor microenvironment. The pH-induced aggregation of PHHPEG6 NFs resulted in enhanced 1O2 generation efficiency and prolonged tumor retention, thus enabling control over the entire PDT process, from the visualization of photosensitizer accumulation to actual PDT and subsequent assessment of the efficacy of the treatment.

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Photodynamic therapy (PDT) is a highly promising therapeutic modality for cancer treatment. The development of stimuli-responsive photosensitizer nanomaterials overcomes certain limitations in clinical PDT. Herein, we report the rational design of a highly sensitive PEGylated photosensitizer-peptide nanofiber (termed PHHPEG6 NF) that selectively aggregates in the acidic tumor and lysosomal microenvironment. These nanofibers exhibit acid-induced enhanced singlet oxygen generation, cellular uptake, and PDT efficacy in vitro, as well as fast tumor accumulation, long-term tumor imaging capacity and effective PDT in vivo. Moreover, based on the prolonged presence of the fluorescent signal at the tumor site, we demonstrate that PHHPEG6 NFs can also be applied for prognostic monitoring of the efficacy of PDT in vivo, which would potentially guide cancer treatment. Therefore, these multifunctional PHHPEG6 NFs allow control over the entire PDT process, from visualization of photosensitizer accumulation, via actual PDT to the assessment of the efficacy of the treatment.

Full Access Link: Angewandte Chemie - International Edition