Acid‐Activatable Transmorphic Peptide‐Based Nanomaterials for Photodynamic Therapy

• Published in: Angewandte Chemie International Edition Vol. 59; no. 46; pp. 20582 - 20588
• Main Authors: Sun, Bingbing, Chang, Rui, Cao, Shoupeng, Yuan, Chengqian, Zhao, Luyang, Yang, Haowen, Li, Junbai, Yan, Xuehai, Hest, Jan C. M.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 09.11.2020; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Acids - chemistry; Assemblies; Biomaterials; Biomedical materials; Chemistry; Chemistry, Multidisciplinary; fibrillar transformation; Fibrils; Fluorescence; Humans; Hydrogen bonds; Hydrogen-Ion Concentration; Morphology; Nanofibers; Nanomaterials; Nanoparticles; Nanostructures - chemistry; Nanotechnology; Peptides; Peptides - chemistry; Photochemotherapy - methods; Photodynamic therapy; photosensitizers; Photosensitizing Agents - chemistry; Physical Sciences; Porphyrins; Porphyrins - chemistry; Retention; Science & Technology; self-assembly; Singlet oxygen; Spectrum Analysis - methods; Tumor Microenvironment; Tumors; self-assembly; NANOPARTICLES; fibrillar transformation; photodynamic therapy; RETENTION; PH; peptides; photosensitizers; PI-PI-STACKING; ELECTROSTATIC REPULSION; COMBINATION; CANCER
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202008708

Inspired by the dynamic morphology control of molecular assemblies in biological systems, we have developed pH‐responsive transformable peptide‐based nanoparticles for photodynamic therapy (PDT) with prolonged tumor retention times. The self‐assembled peptide–porphyrin nanoparticles transformed into nanofibers when exposed to the acidic tumor microenvironment, which was mainly driven by enhanced intermolecular hydrogen bond formation between the protonated molecules. The nanoparticle transformation into fibrils improved their singlet oxygen generation ability and enabled high accumulation and long‐term retention at tumor sites. Strong fluorescent signals of these nanomaterials were detected in tumor tissue up to 7 days after administration. Moreover, the peptide assemblies exhibited excellent anti‐tumor efficacy via PDT in vivo. This in situ fibrillar transformation strategy could be utilized to design effective stimuli‐responsive biomaterials for long‐term imaging and therapy. Fibrillar‐transformable peptide‐porphyrin (PWG) nanoparticles activated by the acidic inter‐ and intracellular tumor microenvironment were developed for photodynamic therapy (PDT). The transformation of nanoparticles into nanofibers improved their singlet oxygen generation ability and enabled high accumulation and long‐term retention at tumor sites, resulting in excellent anti‐tumor efficacy via PDT in vivo.