Publications by authors named "Qingxin Yao"

12 Publications

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Redox-Mediated Reversible Supramolecular Assemblies Driven by Switch and Interplay of Peptide Secondary Structures.

Biomacromolecules 2021 May 7. Epub 2021 May 7.

CAS Center of Excellence for Nanoscience, Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

The construction of reversible supramolecular self-assembly remains a significant challenge. Here, we demonstrate the redox-triggered reversible supramolecular self-assembly governed by the "check and balance" of two secondary conformations within a brushlike peptide-selenopolypeptide conjugate. The conjugate constitutes a polypeptide backbone whose side chain contains selenoether functional moieties and double bonds to be readily grafted with β-sheet-prone short-peptide NapFFC. The backbone of the conjugate initially assumes a robust and rigid α-helical conformation, which inhibits the supramolecular assembly of the short peptide in the side chain and yields an overall irregular aggregate morphology under native/reduced conditions. Upon oxidation of the selenoether to more hydrophilic selenoxide, the backbone helix switches to a flexible and disordered conformation, which unleashes the side-chain NapFFC self-assembly into nanofibrils via the adoption of β-sheet conformation. The reversible switch of the supramolecular morphology enables efficient loading and tumor-microenvironment-triggered release of anticancer drugs for cancer treatment with satisfactory efficacy and biocompatibility. The interplay and interaction between two well-defined secondary structures within one scaffold offer tremendous opportunity for the design and construction of functional supramolecular biomaterials.
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http://dx.doi.org/10.1021/acs.biomac.1c00300DOI Listing
May 2021

Pathological environment directed in situ peptidic supramolecular assemblies for nanomedicines.

Biomed Mater 2021 Feb 25;16(2):022011. Epub 2021 Feb 25.

CAS Center of Excellence for Nanoscience, Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, National Center for Nanoscience and Technology, Beijing 100190, People's Republic of China. University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

Peptidic self-assembly provides a powerful method to build biomedical materials with integrated functions. In particular, pathological environment instructed peptidic supramolecular have gained great progress in treating various diseases. Typically, certain pathology related factors convert hydrophilic precursors to corresponding more hydrophobic motifs to assemble into supramolecular structures. Herein, we would like to review the recent progress of nanomedicines based on the development of instructed self-assembly against several specific disease models. Firstly we introduce the cancer instructed self-assembly. These assemblies have exhibited great inhibition efficacy, as well as enhanced imaging contrast, against cancer models both in vitro and in vivo. Then we discuss the infection instructed peptidic self-assembly. A number of different molecular designs have demonstrated the potential antibacterial application with satisfied efficiency for peptidic supramolecular assemblies. Further, we discuss the application of instructed peptidic self-assembly for other diseases including neurodegenerative disease and vaccine. The assemblies have succeeded in down-regulating abnormal Aβ aggregates and immunotherapy. In summary, the self-assembly precursors are typical two-component molecules with (1) a self-assembling motif and (2) a cleavable trigger responsive to the pathological environment. Upon cleavage, the self-assembly occurs selectively in pathological loci whose targeting capability is independent from active targeting. Bearing the novel targeting regime, we envision that the pathological conditions instructed peptidic self-assembly will lead a paradigm shift on biomedical materials.
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http://dx.doi.org/10.1088/1748-605X/abc2e9DOI Listing
February 2021

Gag Protein Oriented Supramolecular Nets as Potential HIV Traps.

Bioconjug Chem 2021 01 6;32(1):106-110. Epub 2021 Jan 6.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.

For HIV/AIDS treatment, the cocktail therapy which uses a combination of anti-retroviral drugs remains the most widely accepted practice. However, the potential drug toxicity, patient tolerability, and emerging drug resistance have limited its long-term efficiency. Here, we design a HIV Gag protein-targeting redox supramolecular assembly (ROSA) system for potential HIV inhibition. An assembling precursor was constructed through conjugation of an oxidation-activatable fluorogenic compound BQA with a selected tetrapeptide GGFF. Since BQA shares a similar structure with the known Gag inhibitor, the precursor could bind to HIV Gag protein with moderate affinity. Moreover, after oxidation, the corresponding nanofibers could bind to Gag protein and trap HIV to realize virus control, thus providing a potential anti-HIV strategy.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00706DOI Listing
January 2021

Pathological environment directedpeptidic supramolecular assemblies for nanomedicines.

Biomed Mater 2020 Oct 20. Epub 2020 Oct 20.

National Center for Nanoscience and Technology, Haidian District, 100190, CHINA.

Peptidic self-assembly provides a powerful method to build biomedical materials with integrated functions. In particular, pathological environment instructed peptidic supramolecular have gained great progress in treating various diseases. Typically, certain pathology related factors convert hydrophilic precursors to corresponding more hydrophobic motifs to assemble into supramolecular structures. Herein, we would like to review the recent progress of nanomedicines based on the development of instructed self-assembly against several specific disease models. Firstly we introduce the cancer instructed self-assembly. These assemblies have exhibited great inhibition efficacy, as well as enhanced imaging contrast, against cancer models both in vitro and in vivo. Then we discuss the infection instructed peptidic self-assembly. A number of different molecular designs have demonstrated the potential antibacterial application with satisfied efficiency for peptidic supramolecular assemblies. Further, we discuss the application of instructed peptidic self-assembly for other diseases including neurodegenerative disease and vaccine. The assemblies have succeeded in down-regulating abnormal Aβ aggregates and immunotherapy. In summary, the self-assembly precursors are typical two-component molecules with (1) a self-assembling motif and (2) a cleavable trigger responsive to the pathological environment. Upon cleavage, the self-assembly occurs selectively in pathological loci whose targeting capability is independent from active targeting. Bearing the novel targeting regime, we envision that the pathological conditions instructed peptidic self-assembly will lead a paradigm shift on biomedical materials.
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http://dx.doi.org/10.1088/1748-605X/abc2e9DOI Listing
October 2020

Supramolecular assemblies mimicking neutrophil extracellular traps for MRSE infection control.

Biomaterials 2020 09 15;253:120124. Epub 2020 May 15.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Neutrophil extracellular traps (NETs) stick to bacteria and prevent infections in vivo, whose activation is upon inflammatory stimuli along with the sudden increase of reactive oxygen species (ROS). Nevertheless, the risky over activation in NETosis may result in deleterious outcome. A big challenge in using NETs for therapeutics is to synthesize an artificial system that can function as NETs in vivo. Here, we developed an in vivo supramolecular assembly system to imitate the innate immune process of NETs to inhibit methicillin-resistant staphylococcus epidermidis (MRSE) infection. Our synthesized small molecules undergo oxidation to form supramolecular nanofibers at inflammatory loci. The in situ formed nanofibers network efficiently traps MRSE cells and prevent them from aggressive dissemination. The extended interactions between nanofibers and bacteria directly result in the death of MRSE via the transcriptomes alterations. In clinically relevant models (intraperitoneal infection and catheter implantation), our supramolecular nets show significant antibacterial activity, yielding a three times efficacy comparing to vancomycin. The spontaneous consumption of ROS and the formation of antibacterial networks create a steady negative feedback system to combat bacterial infections.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120124DOI Listing
September 2020

Dynamic Detection of Active Enzyme Instructed Supramolecular Assemblies Super-Resolution Microscopy.

ACS Nano 2020 04 6;14(4):4882-4889. Epub 2020 Apr 6.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China.

Inspired by the self-assembly phenomena in nature, the instructed self-assembly of exogenous small molecules in a biological environment has become a prevalent process to control cell fate. Despite mounting examples of versatile bioactivities, the underlying mechanism remains less understood, which is in large hindered by the difficulties in the identification of those dynamic assemblies . Here, with direct stochastic optical reconstruction microscopy, we are able to elucidate the dynamic morphology transformation of the enzyme-instructed supramolecular assemblies inside cancer cells with a resolution below 50 nm. It indicates that the assembling molecules endure drastically different pathways between cell lines with different phosphatase activities and distribution. In HeLa cells, the direct formation of intracellular supramolecular nanofibers showed slight cytotoxicity, which was due to the possible cellular secretory pathway to excrete those exogenous molecules assemblies. In contrast, in Saos-2 cells with active phosphatase on the cell surface, assemblies with granular morphology first formed on the cell membranes, followed by a transformation into nanofibers and accumulation in cells, which induced Saos-2 cell death eventually. Overall, we provided a convenient method to reveal the dynamic nanomorphology transformation of the supramolecular assemblies in a biological environment, in order to decipher their diverse biological activities.
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http://dx.doi.org/10.1021/acsnano.0c00883DOI Listing
April 2020

Synergistic enzymatic and bioorthogonal reactions for selective prodrug activation in living systems.

Nat Commun 2018 11 28;9(1):5032. Epub 2018 Nov 28.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China.

Adverse drug reactions (ADRs) restrict the maximum doses applicable in chemotherapy, which leads to failure in cancer treatment. Various approaches, including nano-drug and prodrug strategies aimed at reducing ADRs, have been developed, but these strategies have their own pitfalls. A renovated strategy for ADR reduction is urgently needed. Here, we employ an enzymatic supramolecular self-assembly process to accumulate a bioorthogonal decaging reaction trigger inside targeted cancer cells, enabling spatiotemporally controlled, synergistic prodrug activation. The bioorthogonally activated prodrug exhibits significantly enhanced potency against cancer cells compared with normal cells. This prodrug activation strategy further demonstrates high tumour inhibition efficacy with satisfactory biocompatibility, pharmacokinetics, and safety in vivo. We envision that integration of enzymatic and bioorthogonal reactions will serve as a general small-molecule-based strategy for alleviation of ADRs in chemotherapy.
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http://dx.doi.org/10.1038/s41467-018-07490-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261997PMC
November 2018

Enzyme-Instructed Supramolecular Self-Assembly with Anticancer Activity.

Adv Mater 2019 Nov 16;31(45):e1804814. Epub 2018 Nov 16.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.

Cancer remains one of the leading causes of death, which has continuously stimulated the development of numerous functional biomaterials with anticancer activities. Herein is reviewed one recent trend of biomaterials focusing on the advances in enzyme-instructed supramolecular self-assembly (EISA) with anticancer activity. EISA relies on enzymatic transformations to convert designed small-molecular precursors into corresponding amphiphilic residues that can form assemblies in living systems. EISA has shown some advantages in controlling cell fate from three aspects. 1) Based on the abnormal activity of specific enzymes, EISA can differentiate cancer cells from normal cells. In contrast to the classical ligand-receptor recognition, the targeting capability of EISA relies on dynamic control of the self-assembly process. 2) The interactions between EISA and cellular components directly disrupt cellular processes or pathways, resulting in cell death phenotypes. 3) EISA spatiotemporally controls the distribution of therapeutic agents, which boosts drug delivery efficiency. Therefore, with regard to the development of EISA, the aim is to provide a perspective on the future directions of research into EISA as anticancer theranostics.
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http://dx.doi.org/10.1002/adma.201804814DOI Listing
November 2019

Hydrogen sulfide induced supramolecular self-assembly in living cells.

Chem Commun (Camb) 2018 Aug 27;54(65):9051-9054. Epub 2018 Jul 27.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China. and University of Chinese Academy of Sciences, Beijing 100049, P. R. China.

Here we developed a critical gasotransmitter (HS) mediated reduction to induce supramolecular self-assembly in multiple living cell lines. Specifically, the reduction converted an azido group to an amine which allowed the formation of intramolecular hydrogen bonds. The hydrogen bonds planarized the assembling molecules and promoted the supramolecular self-assembly.
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http://dx.doi.org/10.1039/c8cc05174gDOI Listing
August 2018

Redox supramolecular self-assemblies nonlinearly enhance fluorescence to identify cancer cells.

Chem Commun (Camb) 2018 May;54(42):5385-5388

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.

Based on the nonlinear fluorescence enhancement, our H2O2 induced supramolecular self-assembly reveals a H2O2 threshold among multiple cancer and normal cells. Oxidative elimination restores an intramolecular hydrogen bond which can planarize the molecule to generate a fluorophore. The planarization enhances the intermolecular π-π stacking to promote self-assembly.
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http://dx.doi.org/10.1039/c8cc02648cDOI Listing
May 2018

Determination of the packing model of a supramolecular nanofiber via mass-per-length measurement and de novo simulation.

Nanoscale 2018 Feb;10(8):3990-3996

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China.

Herein, we report an example of using scanning transmission electron microscopy to determine the mass-per-length of supramolecular nanofibers. Together with the measurement of the diameter of nanofibers via transmission electron microscopy, we could estimate the packing density of assembling molecules along the nanofibers. A parallel unbiased de novo simulation screens and reveals the most plausible molecular packing pattern of small molecules along the supramolecular nanofibers. Remarkably, the simulated packing patterns and density correlate well with the experimental measurements. Unexpectedly, the naphthalene groups are likely facing outward, creating a hydrophobic surface, which is driven by the geometry of the hydrogelator molecule. Overall, this study establishes a complementary method to determine molecular arrangement along the supramolecular nanofibers, which is potentially useful for the guidance of rational design of biomaterials based on self-assembly.
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http://dx.doi.org/10.1039/c8nr00031jDOI Listing
February 2018

Enzyme-Instructed Self-assembly in Biological Milieu for Theranostics Purpose.

Curr Med Chem 2019 ;26(8):1351-1365

Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing 100190, China.

Precision medicine is in an urgent need for public healthcare. Among the past several decades, the flourishing development in nanotechnology significantly advances the realization of precision nanomedicine. Comparing to well-documented nanoparticlebased strategy, in this review, we focus on the strategy using enzyme instructed selfassembly (EISA) in biological milieu for theranostics purpose. In principle, the design of small molecules for EISA requires two aspects: (1) the substrate of enzyme of interest; and (2) self-assembly potency after enzymatic conversion. This strategy has shown its irreplaceable advantages in nanomedicne, specifically for cancer treatments and Vaccine Adjuvants. Interestingly, all the reported examples rely on only one kind of enzymehydrolase. Therefore, we envision that the application of EISA strategy just begins and will lead to a new paradigm in nanomedicine.
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http://dx.doi.org/10.2174/0929867324666170921104010DOI Listing
June 2019