Noncanonical Amino Acids Dictate Peptide Assembly in Living Cells DOI
Xin Liu, Binbin Hu, Zhilin Yu

et al.

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

ConspectusEmulating the structural features or functions of natural systems has been demonstrated as a state-of-the-art strategy to create artificial functional materials. Inspired by assembly and bioactivity proteins, self-assembly peptides into nanostructures represents promising approach for creating biomaterials. Conventional assembled peptide biomaterials are typically formulated in solution delivered pathological sites implementing theranostic objectives. However, this translocation entails switch from formulation conditions physiological environment raises concerns about material performance. In addition, precise efficient accumulation administered at target remains significant challenge, leading potential biosafety issues associated with off-target effects. These limitations significantly hinder progress advanced To address these concerns, past few years have witnessed development situ living new endeavor optimizing biomaterial performance benefiting advances stimuli-responsive reactions regulating noncovalent interactions. refers processes via sites. Due advantages precisely forming well-defined lesions, situ-formed assemblies integrated interesting next-generation biomedical agents.Despite great developing agents, research area still suffers limited toolkit operating under complicated conditions. Considering amino acids being incorporated backbones modified units, an acid is concern. Therefore, our laboratory intensively engaged designing discovering noncanonical (ncAAs) expand manipulating various biological Thus far, we synthesized containing ncAAs 4-aminoproline, 2-nitroimidazole alanine, Se-methionine, sulfated tyrosine, glycosylated serine, which allow us develop acid-responsive, redox-responsive, enzyme-responsive systems. Based on ncAAs, established complex self-sorting assembly, self-amplified dissipative cells optimize peptides. The resulting exhibit morphological adaptability microenvironment, contributes overcoming delivery barriers improvement targeting accumulation. utilizing developed toolkit, further created supramolecular PROTACs, antagonists, probes cancer treatment diagnosis highlight implications usage. Account, summarize journey emphasis mechanism Eventually, also provide forward conceiving prospects challenges clinical translation situ-formulated

Language: Английский

Twin-Tail Tadpole-Shaped Ce6-Peptide Conjugate for Enhanced Photodynamic Cancer Therapy DOI
Mengmeng Jiang,

Shaowen Wu,

Hongxia Zhang

et al.

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Despite its therapeutic potential, photodynamic therapy faces several key limitations in clinical applications, including poor drug delivery and insufficient tumor selectivity. We engineered RFYFYR-Ce6-RFYFYR (R-Ce6-R), a twin-tail peptide–photosensitizer conjugate that self-assembles into nanostructures for improved cancer treatment. By incorporating arginine-rich peptide sequences, this design not only enhances cellular internalization but also promotes peroxynitrite (ONOO–) formation, amplifying the effect. Our studies revealed R-Ce6-R achieves 33-fold higher potency than unmodified Ce6, with an IC50 of 0.18 μM. The demonstrated selective accumulation tissue, robust ROS generation, complete regression animal models while maintaining favorable safety profile. These results establish as innovative approach advancing

Language: Английский

Citations

0
Noncanonical Amino Acids Dictate Peptide Assembly in Living Cells DOI
Xin Liu, Binbin Hu, Zhilin Yu

et al.

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

ConspectusEmulating the structural features or functions of natural systems has been demonstrated as a state-of-the-art strategy to create artificial functional materials. Inspired by assembly and bioactivity proteins, self-assembly peptides into nanostructures represents promising approach for creating biomaterials. Conventional assembled peptide biomaterials are typically formulated in solution delivered pathological sites implementing theranostic objectives. However, this translocation entails switch from formulation conditions physiological environment raises concerns about material performance. In addition, precise efficient accumulation administered at target remains significant challenge, leading potential biosafety issues associated with off-target effects. These limitations significantly hinder progress advanced To address these concerns, past few years have witnessed development situ living new endeavor optimizing biomaterial performance benefiting advances stimuli-responsive reactions regulating noncovalent interactions. refers processes via sites. Due advantages precisely forming well-defined lesions, situ-formed assemblies integrated interesting next-generation biomedical agents.Despite great developing agents, research area still suffers limited toolkit operating under complicated conditions. Considering amino acids being incorporated backbones modified units, an acid is concern. Therefore, our laboratory intensively engaged designing discovering noncanonical (ncAAs) expand manipulating various biological Thus far, we synthesized containing ncAAs 4-aminoproline, 2-nitroimidazole alanine, Se-methionine, sulfated tyrosine, glycosylated serine, which allow us develop acid-responsive, redox-responsive, enzyme-responsive systems. Based on ncAAs, established complex self-sorting assembly, self-amplified dissipative cells optimize peptides. The resulting exhibit morphological adaptability microenvironment, contributes overcoming delivery barriers improvement targeting accumulation. utilizing developed toolkit, further created supramolecular PROTACs, antagonists, probes cancer treatment diagnosis highlight implications usage. Account, summarize journey emphasis mechanism Eventually, also provide forward conceiving prospects challenges clinical translation situ-formulated

Language: Английский

Citations

0