Aspartate Isomerization Regulates in Situ Assembly of Peptides into Supramolecular Probes for Detection of Protein Carboxyl Methyltransferase in Bladder Cancer DOI
Zeyu Zhang, Xin Liu, Feng Tian

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Protein carboxyl methyltransferase (PCMT) restores aspartate isomers in proteins and plays a critical role cancer prognosis. However, vivo detection of PCMT remains challenging. Here, we report the isomerization-regulated situ assembly peptides into supramolecular probes within living cells for bladder cancer. The peptide consists alternating hydrophobic hydrophilic residues contains an isoAsp residue as kinked site to prevent facial amphiphilicity peptide. Exposure converts Asp peptide, thereby promoting its nanofibers. Incorporation 7-nitro-2,1,3-benzoxadiazole (NBD) nanofibers enables based on hydrophobicity-dependent fluorescence NBD units. Both cellular animal studies confirm capability efficient PCMT. Our finding demonstrates strategy regulating systems thus provides new tool creation biomedical agents future.

Language: Английский

Sulfatase-Induced In Situ Formulation of Antineoplastic Supra-PROTACs DOI

Ninglin Chen,

Zeyu Zhang, Xin Liu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10753 - 10766

Published: April 5, 2024

Proteolysis targeting chimera (PROTAC) technology is an innovative strategy for cancer therapy, which, however, suffers from poor delivery and limited capability protein of interest (POI) degradation. Here, we report a the in situ formulation antineoplastic Supra-PROTACs via intracellular sulfatase-responsive assembly peptides. Coassembling sulfated peptide with two ligands binding to ubiquitin VHL Bcl-xL leads formation pro-Supra-PROTAC, which ratio rationally optimized based on their affinity. The resulting pro-Supra-PROTAC precisely undergoes enzyme-responsive into nanofibrous cells overexpressing sulfatase. Mechanistic studies reveal that pro-Supra-PROTACs selectively cause apparent cytotoxicity through degradation activation caspase-dependent apoptosis, during ligand improves bioactivity POI cell death. In vivo show enhanced tumor accumulation retention pro-Supra-PROTACs, as well inhibiting growth excellent biosafety when coadministrating chemodrugs. Our findings provide new approach enzyme-regulated peptides living development PROTACs high delivering efficiency.

Language: Английский

Citations

20

Physical strategies to engineer supramolecular composite hydrogels for advanced biomedical applications DOI

Sravan Baddi,

Auphedeous Y. Dang-i,

Fengli Gao

et al.

Progress in Materials Science, Journal Year: 2025, Volume and Issue: 151, P. 101428 - 101428

Published: Jan. 9, 2025

Language: Английский

Citations

4

A comprehensive review on peptide-bearing biomaterials: From ex situ to in situ self-assembly DOI
Si‐Yong Qin, Jiaqi Feng, Yin‐Jia Cheng

et al.

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 502, P. 215600 - 215600

Published: Dec. 14, 2023

Language: Английский

Citations

40

Hierarchical assembly of intrinsically disordered short peptides DOI Creative Commons
Jiaqi Guo, Shane T. Rich-New, Chen Liu

et al.

Chem, Journal Year: 2023, Volume and Issue: 9(9), P. 2530 - 2546

Published: May 16, 2023

Language: Английский

Citations

29

Unnatural Peptide Assemblies Rapidly Deplete Cholesterol and Potently Inhibit Cancer Cells DOI
Qiuxin Zhang, Weiyi Tan, Zhiyu Liu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(19), P. 12901 - 12906

Published: May 3, 2024

Cholesterol-rich membranes play a pivotal role in cancer initiation and progression, necessitating innovative approaches to target these for inhibition. Here we report the first case of unnatural peptide (1) assemblies capable depleting cholesterol inhibiting cells. Peptide 1 self-assembles into micelles is rapidly taken up by cells, especially when combined with an acute cholesterol-depleting agent (MβCD). Click chemistry has confirmed that depletes cell membrane cholesterol. It localizes membrane-rich organelles, including endoplasmic reticulum, Golgi apparatus, lysosomes. Furthermore, potently inhibits malignant working synergistically cholesterol-lowering agents. Control experiments have C-terminal capping amino acid residues (i.e., BiP) are essential both depletion potent This work highlights as promising platform targeting controlling fates.

Language: Английский

Citations

15

Intracellular Chemical Reaction‐Induced Self‐Assembly for the Construction of Artificial Architecture and Its Functions DOI Creative Commons

Sangpil Kim,

Gaeun Park, Dohyun Kim

et al.

Advanced NanoBiomed Research, Journal Year: 2024, Volume and Issue: 4(4)

Published: Feb. 6, 2024

Intracellular assemblies play vital roles in maintaining cellular functions through structural recognition‐mediated interactions. The introduction of artificial structures has garnered substantial interest modulating via activation/inhibition interactions with biomacromolecules. However, the uptake these high‐molecular‐weight may limit their performance. Recently, intracellular chemical‐reaction‐induced self‐assembly emerged as a promising strategy for generating situ nanostructures biofunctionalities interacting This approach addresses challenge synthetic reactions occurring complex environments by utilizing diverse chemical that respond to endogenous and exogenous stimuli. review provides an overview latest advancements techniques. It focuses on responsiveness specific conditions, such redox overexpressed enzymes. Additionally, initiation stimuli, including reagents irradiation is explored. Polymerization‐induced hydrophobicity highlighted, leading into micro‐/nanostructures. These processes contribute construction materials morphologies, offering versatile functionalities biological applications.

Language: Английский

Citations

10

Chemical Reactions in Living Systems DOI Creative Commons
Dominik Schauenburg, Tanja Weil

Advanced Science, Journal Year: 2023, Volume and Issue: 11(8)

Published: Sept. 7, 2023

Abstract The term “in vivo (“in the living”) chemistry” refers to chemical reactions that take place in a complex living system such as cells, tissue, body liquids, or even an entire organism. In contrast, occur generally outside organisms artificial environment (e.g., test tube) are referred vitro. Over past decades, significant contributions have been made this rapidly growing field of chemistry, but it is still not fully understood, which transformations proceed efficiently without formation by‐products how product environments can be characterized. Potential applications imagined synthesize drug molecules directly within cell confer new cellular functions through controlled will improve understanding systems and develop therapeutic strategies. guiding principles contribution twofold: 1) Which translated from laboratory system? 2) characterization methods suitable for studying structure environments?

Language: Английский

Citations

18

Organelle-Mediated Dissipative Self-Assembly of Peptides in Living Cells DOI
Hao Wang, Yanqiu Song, Weishu Wang

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(1), P. 330 - 341

Published: Dec. 19, 2023

Implementing dissipative assembly in living systems is meaningful for creation of materials or even artificial life. However, intracellular remains scarce and significantly impeded by the challenges lying precisely operating chemical reaction cycles under complex physiological conditions. Here, we develop organelle-mediated self-assembly peptides cells fueled GSH, via design a mitochondrion-targeting redox-responsive hexapeptide. While hexapeptide undergoes efficient self-assembly, addition GSH into peptide solution presence mitochondrion-biomimetic liposomes containing hydrogen peroxide allows transient peptides. Internalization LPS-stimulated macrophages leads to driven reduction association assemblies with mitochondria. The facilitates reversible oxidation reduced mitochondrion-residing ROS thereby dissociates from mitochondria re-enter cytoplasm reduction. metastable peptide–mitochondrion complexes prevent thermodynamically equilibrated thus establishing stimulated macrophages. entire self-assembling process elimination elevated decrease pro-inflammatory cytokine expression. Creating assisted internal structures provides new avenues development medical agents future.

Language: Английский

Citations

18

From cells to subcellular organelles: Next-generation cancer therapy based on peptide self-assembly DOI
Huayang Liu, Huaimin Wang

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 209, P. 115327 - 115327

Published: May 3, 2024

Language: Английский

Citations

9

A Coupling‐Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells DOI Open Access

Ben‐Li Song,

Jiaqi Wang,

Guangxu Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(45)

Published: July 24, 2024

Abstract The strategy of in vivo self‐assembly has been developed for improved enrichment and long‐term retention anticancer drug tumor tissues. However, most self‐assemblies with non‐covalent bonding interactions are susceptible to complex physiological environments, leading weak stability loss biological function. Here, we develop a coupling‐induced assembly (CIA) generate covalently crosslinked nanofibers, which is applied situ constructing artificial shell on mitochondria. oxidation‐responsive peptide‐porphyrin conjugate P1 synthesized, self‐assemble into nanoparticles. Under the oxidative microenvironment mitochondria, coupling thiols causes formation dimers, further ordered stacked nanofibers. As result, constructed mitochondria efficiently through multivalent cooperative due increased binding sites. ultrasound (US) irradiation, porphyrin molecules produce large amount reactive oxygen species (ROS) that act adjacent mitochondrial membrane, exhibiting ~2‐fold higher antitumor activity than nanoparticles vitro vivo. Therefore, mitochondria‐targeted CIA provides novel perspective sonodynamic therapy (SDT) shows potential applications therapies.

Language: Английский

Citations

8