Publications by authors named "Guangqi Wu"

6 Publications

  • Page 1 of 1

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

Biomacromolecules 2021 Jun 7;22(6):2563-2572. 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
June 2021

DNA Origami-Enabled Engineering of Ligand-Drug Conjugates for Targeted Drug Delivery.

Small 2020 04 19;16(16):e1904857. Epub 2020 Mar 19.

School of Chemistry and Chemical Engineering and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

Effective drug delivery systems that can systematically and selectively transport payloads to disease cells remain a challenge. Here, a targeting ligand-modified DNA origami nanostructure (DON) as an antibody-drug conjugate (ADC)-like carrier for targeted prostate cancer therapy is reported. Specifically, DON of six helical bundles is modified with a ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) against prostate-specific membrane antigen (PSMA), to serve as the antibody for drug conjugation in ADC. Doxorubicin (Dox) is then loaded to DON through intercalation to dsDNA. This platform features in spatially controllable organization of targeting ligands and high drug loading capacity. With this nanocomposite, selective delivery of Dox to the PSMA+ cancer cell line LNCaP is readily achieved. The consequent therapeutic efficacy is critically dependent on the numbers of targeting ligand assembled on DON. This target-specific and biocompatible drug delivery platform with high maximum tolerated doses shows immense potential for developing novel nanomedicine.
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http://dx.doi.org/10.1002/smll.201904857DOI Listing
April 2020

PEGylated gene carriers in serum under shear flow.

Soft Matter 2020 Mar;16(9):2301-2310

Beijing National Laboratory for Molecular Sciences and the Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

The behaviour of drug/gene carriers in the blood stream under shear is still a puzzle. In this work, using the complexes formed by 21 bp DNA and poly(ethylene glycol)-b-poly(l-lysine) (PEG-PLL) of varying PEG lengths, we studied the dynamic behaviour of the complexes in the presence of fetal bovine serum (FBS) and under flow at different shear rates, a condition mimicking the internal physical environment of blood vessels. The PEG5k-PLL/DNA complex possesses a dense DNA/PLL core and a loose PEG5k protecting layer. The PEGylated DNA complexes exhibit multiple responses to external shear in the presence of FBS. The loose PEG5k layer is firstly disturbed at a shear rate below 30 s-1. The exposure of the charged core to the environment results in a secondary aggregation of the complex with FBS. The size of the aggregate is limited to a certain range as the shear rate increases to 50 s-1. The dense DNA/PLL core starts to withstand the shear force as the shear rate reaches 500 s-1. The reorganization of the core to accommodate more serum molecules leads to tertiary aggregation of the complexes. If PEG cannot form a valid layer around the complex, as in PEG2k-PLL/DNA, the complex forms an aggregate even without shear, and the first shear dependent region is missing. If the PEG layer is too stable around the complex, as in PEG10k-PLL/DNA, no tertiary aggregation occurs. The mechanism of shear on the behaviour of delivery particles in serum helps to design gene carriers with high efficacy.
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http://dx.doi.org/10.1039/c9sm02397fDOI Listing
March 2020

Synthesis of water soluble and multi-responsive selenopolypeptides via ring-opening polymerization of N-carboxyanhydrides.

Chem Commun (Camb) 2019 Jul;55(54):7860-7863

Beijing National Laboratory for Molecular Sciences, Center for Soft Matter Science and Engineering, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, People's Republic of China.

We report here the synthesis of water soluble selenopolypeptides via the ring-opening polymerization of N-carboxyanhydrides. The oligoethylene glycol-bearing selenopolypeptides are thermally responsive in aqueous solutions with tunable lower critical solution temperatures. The polymers can also undergo rapid and reversible helix-coil transitions upon responding to the added redox cycle.
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http://dx.doi.org/10.1039/c9cc03767eDOI Listing
July 2019

Topology- and linking number-controlled synthesis of a closed 3 link chain of single-stranded DNA.

Chem Commun (Camb) 2018 Sep;54(72):10156-10159

College of Food Science and Engineering, Ocean University of China, Nucleic Acids Chemistry and Biotechnology Laboratory, No. 5 Yushan Road, Shinan-qu, Qingdao 266003, China.

In spite of remarkable progress in synthetic methodology, a closed three-link chain (one of the simplest but the most important topological isomers of [3]catenane) has never been prepared. Here we synthesized this isomer in high yield from three oligonucleotides which are designed to optimize various chemical and steric factors in their mutual hybridization.
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http://dx.doi.org/10.1039/c8cc04965cDOI Listing
September 2018

Efficient Synthesis of Topologically Linked Three-Ring DNA Catenanes.

Chembiochem 2016 06 23;17(12):1127-31. Epub 2016 May 23.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China.

Topologically controlled DNA catenanes are promising elements for the construction of molecular machines but present a significant effort in DNA nanotechnology. We report an efficient approach for preparing linear three-ring catenanes (L3C) composed of single-stranded DNA. The linking number was strictly controlled by using short complementary regions (6 nt) between each two DNA rings. High efficiency of forming three-ring catenanes (yield as high as 63 %) was obtained by using an 80 nt oligonucleotide as the scaffold to draw close the three pre-rings for hybridization between short complementary DNA. After assembly, three pre-rings were closed by DNA ligation using three 12 nt oligonucleotides as splints to form interlocked three-ring catenanes. L3C nanostructures were imaged in air by AFM: the catenane exhibited a smooth circular shape and was arranged in a line with well-defined structure, as expected.
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http://dx.doi.org/10.1002/cbic.201600071DOI Listing
June 2016