Enzyme-Instructed Assembly and Disassembly Processes for Targeting Downregulation in Cancer Cells

Feng, Zhaoqianqi; Wang, Huaimin; Zhou, Rong; Li, Jie; Xu, Bing

doi:10.1021/jacs.7b00070

Cited by 133 publications

(108 citation statements)

References 41 publications

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“…Moreover, the combination of enzyme-instructed assembly and disassembly affords a reaction cycle to switch between the monomers and assemblies, 19 as well as an approach to target downregulation (or loss of functions) in cancer cells. 20 Hamachi and coworkers demonstrated the coupling of enzymatic reactions with stimuli responsive hydrogels for logic-gate sensing of disease-related biomarkers. 21 Besides the enzymes, photocatalysts 22 serve as simple tools to control the rates of the formation and breaking of assemblies via the incorporation of catalytically controlled steps in self-assembly processes.…”

Section: Rational Designmentioning

confidence: 99%

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Supramolecular catalysis and dynamic assemblies for medicine

et al. 2017

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In this review, supramolecular catalysis refers to the integration of catalytic process with molecular self-assembly driven by noncovalent interactions, and dynamic assemblies are the assemblies that form and dissipate reversibly. Cells extensively employ supramolecular catalysis and dynamic assemblies for controlling their complex functions. The dynamic generation of supramolecular assemblies of small molecules has made a considerable progress in the last decade, though the disassembly processes remain underexplored. Here, we discuss the regulation of dynamic assemblies via self-assembly and disassembly processes for therapeutics and diagnostics. We first briefly introduce the self-assembly and disassembly processes in the context of cells, which provide the rationale for designing approaches to control the assemblies. Then, we describe recent advances in designing and regulating the self-assembly and disassembly of small molecules, especially for molecular imaging and anticancer therapeutics. Finally, we provide a perspective on future directions of the research on supramolecular catalysis and dynamic assemblies for medicine.

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Section: Rational Designmentioning

confidence: 99%

“…20 As the substrates of both carboxylesterases (CES) and ALP, precursor 15 turns into 16 upon the treatment of ALP, converts into 17 by the ester bond cleavage catalyzed by CES, and generates 18 via the actions of ALP and CES (Fig. 8A).…”

Section: Assembly and Disassemblymentioning

confidence: 99%

Supramolecular catalysis and dynamic assemblies for medicine

et al. 2017

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“…Fore xample,t he dephosphorylation/phosphorylation cycle catalyzed by the ALP/kinase switch has been applied to control the selfassembly of amphiphilic peptides, [5] nanoparticles, [13] and block copolymers. [15] Liang and coworkers also demonstrated acell-environment-differentiated molecular self-assembly with an anofiber-to-nanofiber transformation by an ALP-triggered dephosphorylation and aG SH-triggered condensation reaction. [15] Liang and coworkers also demonstrated acell-environment-differentiated molecular self-assembly with an anofiber-to-nanofiber transformation by an ALP-triggered dephosphorylation and aG SH-triggered condensation reaction.…”

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confidence: 99%

Tandem Molecular Self‐Assembly in Liver Cancer Cells

Zhan

Cai

et al. 2018

Angewandte Chemie

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We herein describe the tandem molecular selfassembly of ap eptide derivative (1)t hat is controlled by ac ombination of enzymatic and chemical reactions.I n phosphate-buffered saline (PBS), compound 1 self-assembles first into nanoparticles by phosphatase and then into nanofibers by glutathione.Liver cancer cells exhibit higher concentrations of both phosphatase and GSH than normal cells. Therefore,t he tandem self-assembly of 1 also occurs in the liver cancer cell lines HepG2 and QGY7703;compound 1 first forms nanoparticles around the cells and then forms nanofibers inside the cells.Owing to this self-assembly mechanism, compound 1 exhibits large ratios for cellular uptake and inhibition of cell viability between liver cancer cells and normal liver cells.W ee nvision that using both extracellular and intracellular reactions to trigger tandem molecular self-assembly could lead to the development of supramolecular nanomaterials with improved performance in cancer diagnostics and therapy.Self-assembly is ap owerful tool for preparing supramolecular materials. [1] Assisted by non-covalent interactions,s mall building blocks spontaneously and hierarchically assemble into functional materials. [2] General approaches usually utilize chemical triggers,external energy,and solvent evaporation to trigger the self-assembly process,while biology takes advantage of biocatalysts to generate building blocks in am ore controllable and efficient way.I nspired by nature,c atalytic self-assembly has been widely explored to construct dynamic, [3] dissipative, [4] and reversible [5] nanostructures. These nanostructures not only offer ap latform for understanding the hierarchical self-assembly processes occurring in biological systems but also show promising applications in sensing, [6] drug delivery, [7] cell fate control, [8] immune response manipulation, [9] and regenerative medicine. [10] However,r esearch efforts mainly focus on using as ingle-step reaction catalyzed by an enzyme or on using asmall molecule to trigger the self-assembly process. [11] Although kinetic control has shown pronounced influence on the outcome of single-step self-assembly, [12] multistep self-assembly could lead to more sophisticated and functional materials.Using two reactions to control supramolecular selfassembly has recently attracted research interest. Fore xample,t he dephosphorylation/phosphorylation cycle catalyzed by the ALP/kinase switch has been applied to control the selfassembly of amphiphilic peptides, [5] nanoparticles, [13] and block copolymers. [14] Xu and co-workers recently described the control of amolecular self-assembly by ALP and esterase, which led to the selective inhibition of cancer cell growth through the down-regulation of esterase. [15] Liang and coworkers also demonstrated acell-environment-differentiated molecular self-assembly with an anofiber-to-nanofiber transformation by an ALP-triggered dephosphorylation and aG SH-triggered condensation reaction. [16] Theg roups of Xu and Maruyama have described extracellular [17] an...

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“…1A) as their functional mimics because (i) higher-order assemblies of proteins, with a structural and dynamic continuum, are emerging as a new paradigm in biology to understand cellular functions, [10] but these insights have yet to be applied in designing the next generation biomaterials; (ii) assemblies of small molecules in the cellular milieu exhibit emergent properties. [11] To verify the roles of saccharides and dephosphorylation, we intentionally excluded known cell adhesion sequences in the phosphopeptides or the glycopeptides. We used the ligand-receptor interaction [12] (Fig.…”

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An in situ Dynamic Continuum of Supramolecular Phosphoglycopeptides Enables Formation of 3D Cell Spheroids

et al. 2017

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Higher-order assemblies of proteins, with a structural and dynamic continuum, is an important concept in biology, but these insights have yet to be applied in designing biomaterials. Dynamic assemblies of supramolecular phosphoglycopeptides (sPGPs) transform a 2D cell sheet into 3D cell spheroids. A ligand-receptor interaction between a glycopeptide and a phosphopeptide produces sPGPs that form nanoparticles, which transform into nanofibrils upon partial enzymatic dephosphorylation. The assemblies form dynamically and hierarchically in situ on the cell surface, and interact with the extracellular matrix molecules and effectively abolish contact inhibition of locomotion (CIL) of the cells. Integrating molecular recognition, catalysis, and assembly, these active assemblies act as a dynamic continuum to disrupt CIL, thus illustrating a new kind of biomaterial for regulating cell behavior.

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Enzyme-Instructed Assembly and Disassembly Processes for Targeting Downregulation in Cancer Cells

Cited by 133 publications

References 41 publications

Supramolecular catalysis and dynamic assemblies for medicine

Supramolecular catalysis and dynamic assemblies for medicine

Tandem Molecular Self‐Assembly in Liver Cancer Cells

An in situ Dynamic Continuum of Supramolecular Phosphoglycopeptides Enables Formation of 3D Cell Spheroids

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