In situ oxidation-regulated self-assembly of peptides into transformable scaffolds for cascade therapy

Song, Na; Zhou, Zhenhua; Song, Yanqiu; Li, Mingming; Yu, Xueli; Hu, Binbin; Yu, Zhilin

doi:10.1016/j.nantod.2021.101198

Cited by 26 publications

(23 citation statements)

References 38 publications

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“…This information indicates the formation of multilayered nanoribbons by peptide EVM Se via perpendicular organization along the long axis of the nanoribbons, which is consistent with the conventional structures formed by bolaamphiphilic peptides. 47,52 The nanoribbons with a width of approximately 9.8−50.2 nm were observed in the TEM studies of peptide EVM Se as well (Figure 1D). We also characterized the secondary structures formed by peptides E3C16 and EVM Se via circular dichroism (CD) spectroscopy (Figure 1E).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

In Situ Self-Sorting Peptide Assemblies in Living Cells for Simultaneous Organelle Targeting

Liu

et al. 2022

J. Am. Chem. Soc.

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Self-sorting is a common phenomenon in eukaryotic cells and represents one of the versatile strategies for the formation of advanced functional materials; however, developing artificial self-sorting assemblies within living cells remains challenging. Here, we report on the GSHresponsive in situ self-sorting peptide assemblies within cancer cells for simultaneous organelle targeting to promote combinatorial organelle dysfunction and thereby cell death. The self-sorting system was created via the design of two peptides E3C16E6 and EVM SeO derived from lipidinspired peptide interdigitating amphiphiles and peptide bola-amphiphiles, respectively. The distinct organization patterns of the two peptides facilitate their GSH-induced self-sorting into isolated nanofibrils as a result of cleavage of disulfide-connected hydrophilic domains or reduction of selenoxide groups. The GSH-responsive in situ self-sorting in the peptide assemblies within HeLa cells was directly characterized by super-resolution structured illumination microscopy. Incorporation of the thiol and ER-targeting groups into the self-sorted assemblies endows their simultaneous targeting of endoplasmic reticulum and Golgi apparatus, thus leading to combinatorial organelle dysfunction and cell death. Our results demonstrate the establishment of the in situ self-sorting peptide assemblies within living cells, thus providing a unique platform for drug targeting delivery and an alternative strategy for modulating biological processes in the future.

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Section: ■ Results and Discussionmentioning

confidence: 99%

In Situ Self-Sorting Peptide Assemblies in Living Cells for Simultaneous Organelle Targeting

Liu

et al. 2022

J. Am. Chem. Soc.

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“…The intimate relationship between the structural features of peptide nanostructures and amino acid sequences has been thoroughly elucidated over the past few decades. − This has inspired establishment of various controllable self-assembling peptide systems based on stimuli-responsive reactions of natural or noncanonical amino acids, including redox-, − pH-, − photo-, and enzyme-responsive reactions, − and among others, , for creation of functional materials with great potential in disease diagnosis and treatment. − Among the internal or external stimuli, nitroreductase (NTR) is a flavin-containing enzyme conventionally overexpressed in the hypoxic region of solid tumors and enables one to reduce the nitro groups to (hydroxy)amino groups using NAD(P)H as the electron source . Thus far, a considerable number of NTR-responsive hydrogels, , imaging probes, − drug delivery vehicles, − or activatable prodrugs − have been developed and exhibit broad biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Noncanonical Amino Acids for Hypoxia-Responsive Peptide Self-Assembly and Fluorescence

Song

Cao

et al. 2021

J. Am. Chem. Soc.

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Design of endogenous stimuli-responsive amino acids allows for precisely modulating proteins or peptides under a biological microenvironment and thereby regulating their performance. Herein we report a noncanonical amino acid 2-nitroimidazol-1-yl alanine and explore its functions in creation of the nitroreductase (NTR)-responsive peptide-based supramolecular probes for efficient hypoxia imaging. On the basis of the reduction potential of the nitroimidazole unit, the amino acid was synthesized via the Mitsunobu reaction between 2-nitroimidazole and a serine derivate. We elucidated the relationship between the NTR-responsiveness of the amino acid and the structural feature of peptides involving a series of peptides. This eventually facilitates development of aromatic peptides undergoing NTR-responsive self-assembly by rationally optimizing the sequences. Due to the intrinsic role of 2-nitroimidazole in the fluorescence quench, we created a morphology-transformable supramolecular probe for imaging hypoxic tumor cells based on NTR reduction. We found that the resulting supramolecular probes penetrated into solid tumors, thus allowing for efficient fluorescence imaging of tumor cells in hypoxic regions. Our findings demonstrate development of a readily synthesized and versatile amino acid with exemplified properties in creating fluorescent peptide nanostructures responsive to a biological microenvironment, thus providing a powerful toolkit for synthetic biology and development of novel biomaterials.

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“…Yu and co-workers reported the self-assembly of oxidatively regulated peptides generated by in-situ ROS into a deformable scaffold for cascade cancer treatment. (Song et al, 2021). This ROS-responsive morphology transformable scaffold DPEIM consisted of three parts, hexapeptide EIMIME, photosensitizer chlorin e6 (Ce6) (Ce6-EIM) and chemotherapeutics camptothecin (CPT-EIM).…”

Section: Redox Speciesmentioning

confidence: 99%

Supramolecular Nanomedicines of In-Situ Self-Assembling Peptides

Zhang

Gao

2022

Front. Chem.

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Nanomedicines provide distinct clinical advantages over traditional monomolecular therapeutic and diagnostic agents. Supramolecular nanomedicines made from in-situ self-assembling peptides have emerged as a promising strategy in designing and fabricating nanomedicines. In-situ self-assambly (SA) allows the combination of nanomedicines approach with prodrug approach, which exhibited both advantages of these strategies while addressed the problems of both and thus receiving more and more research attention. In this review, we summarized recently designed supramolecular nanomedicines of in-situ SA peptides in the manner of applications and design principles, and the interaction between the materials and biological environments was also discussed.

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In situ oxidation-regulated self-assembly of peptides into transformable scaffolds for cascade therapy

Cited by 26 publications

References 38 publications

In Situ Self-Sorting Peptide Assemblies in Living Cells for Simultaneous Organelle Targeting

In Situ Self-Sorting Peptide Assemblies in Living Cells for Simultaneous Organelle Targeting

Noncanonical Amino Acids for Hypoxia-Responsive Peptide Self-Assembly and Fluorescence

Supramolecular Nanomedicines of In-Situ Self-Assembling Peptides

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