Responsive Peptide Nanofibers with Theranostic and Prognostic Capacity

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.