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A novel PD-L1 targeting peptide self-assembled nanofibers for sensitive tumor imaging and photothermal immunotherapy in vivo

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Nano Research 2022年第8期15卷 7286-7294页

作者： Linping Fu Jianhu Zhang Chenchen Wu Weizhi Wang Dong Wang Zhiyuan Hu Zihua Wang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Key Laboratory of Standardization and Measurement for NanotechnologyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China School of Nanoscience and Technology Sino-Danish CollegeUniversity of Chinese Academy of SciencesBeijing 100049China Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases School of Basic Medical SciencesFujian Medical UniversityFuzhou 350122China School of Chemical Engineering and Pharmacy Wuhan Institute of TechnologyWuhan 430205China School of Chemistry and Chemical Engineering Beijing Institute of TechnologyBeijing 100081China Center for AIE Research Shenzhen Key Laboratory of Polymer Science and TechnologyGuangdong Research Center for Interfacial Engineering of Functional MaterialsCollege of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China

Programmed death 1(PD-1)and its ligand PD-L1 are two typical immune ***-based immune checkpoint blockade(ICB)strategy targeting PD-1/PD-L1 achieved a significant therapeutic effect on ***,due to the impenetrability of antibody drugs and the occurrence of immune-related adverse events,only a minority of patients benefit from this *** multimerization has been widely proved to be an effective method to improve receptor binding affinity through a multivalent synergistic *** this study,we report a novel peptide-aggregation-induced emission(AIE)hybrid supramolecular TAP,which can self-assemble into nanofibers through non-covalent interactions such as hydrogen bonds,with a specific nanomolar affinity to PD-L1 in vivo and in *** with near-infrared agents,it can be used for tumor imaging and photothermal therapy,which enables photothermal ablation of cancer cells for generating tumor-associated antigen(TAA)and triggering a series of immunological ***,our work suggests that synthetic self-assembled peptide nanofibers can be developed as attractive platforms for active photothermal immunotherapies against cancer.

关键词： programmed death 1(PD-1) targeting peptide self-assembly immune checkpoint blockade photothermal therapy

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Dual targeting to Mitochondria and Chloroplasts： Characterization of Thr-tRNA Synthetase targeting peptide

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Molecular Plant 2009年第6期2卷 1298-1309页

作者： Anna-Karin Berglund Erika Spanning Henrik Biverstahl Gianluca Maddalo Christian Tellgren-Roth Lena Maler Elzbieta Glaser Department of Biochemistry and Biophysics Arrhenius Laboratories for Natural Science Stockholm University SF-10691 Stockholm Sweden Department of Genetics and Pathology Rudbecklaboratoriet Uppsala University SE-751 85 Uppsala Sweden

There is a group of proteins that are encoded by a single gene, expressed as a single precursor protein and dually targeted to both mitochondria and chloroplasts using an ambiguous targeting peptide. Sequence analysis of 43 dual targeted proteins in comparison with 385 mitochondrial proteins and 567 chloroplast proteins ofArabidopsis thaliana revealed an overall significant increase in phenylalanines, leucines, and serines and a decrease in acidic amino acids and glycine in dual targeting peptides （dTPs）. The N-terminal portion of dTPs has significantly more serines than mTPs. The number of arginines is similar to those in mTPs, but almost twice as high as those in cTPs. We have investigated targeting determinants of the dual targeting peptide of Thr-tRNA synthetase （ThrRS-dTP） studying organellar import of N- and C-terminal deletion constructs of ThrRS-dTP coupled to GFR These results show that the 23 amino acid long N-terminal portion of ThrRS-dTP is crucial but not sufficient for the organellar import. The C-terminal deletions revealed that the shortest peptide that was capable of conferring dual targeting was 60 amino acids long. We have purified the ThrRS- dTP（2-60） to homogeneity after its expression as a fusion construct with GST followed by CNBr cleavage and ion exchange chromatography. The purified ThrRS-dTP（2-60） inhibited import of pF1β into mitochondria and of pSSU into chloroplasts at μM concentrations showing that dual and organelle-specific proteins use the same organellar import pathways. Furthermore, the CD spectra of ThrRS-dTP（2-60） indicated that the peptide has the propensity for forming α-helical structure in membrane mimetic environments; however, the membrane charge was not important for the amount of induced helical structure. This is the first study in which a dual targeting peptide has been purified and investigated by biochemical and biophysical means.

关键词： Dual targeting mitochondria chloroplast targeting peptide aminoacyl-tRNA synthetase

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Isolation and identification of targeting peptide to LILRB2

Isolation and identification of targeting peptide to LILRB2

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第九届全国免疫学学术大会

作者： Jie Wang Yuqing Shen Ying Zhang Jing Xia Bo Fu Jianqiong Zhang Key Laboratory of Developmental Genes and Human Diseases Ministry of EducationMedical SchoolSoutheast University

Human leukocyte immunoglobulin-like receptor B2(LILRB2)is part of the B type subfamily of LILR receptors,which consists of five highly homologous family members in *** mice,however,there is a single ortholog,paired immunoglobulin-like receptor B(PirB).LILRB2 contains four Ig-like repeats,as opposed to six Ig-like repeats in PirB *** originally thought to function exclusively in the immune system,are now also known to be expressed by *** the nervous system,more and more observations imply that PirB plays an inhibitory role in neurite outgrowth and restricts neuronal plasticity following CNS injury or ***2 may execute these roles in *** vitro,LILRB2 also acts as functional receptors to inhibit axonal outgrowth on Nogo,myelin-associated glycoprotein,and oligodendrocyte myelin glycoprotein ***2 proteins detected in human brain are receptors for Aβoligomers which are key mediators of cognitive dysfunction in Alzheimer’s disease(AD).So therapies that selectively block LILRB2 function may have a vast potential for treatment of AD or CNS *** goal of our study was to develop a novel peptide that target *** against the recombinant human LILRB2-Fc chimera(R&D system)was performed using the Ph.D.-12 phage display peptide library(New England Biolabs).Three rounds of selection were *** each round,the bound phages were rescued and amplified in ER2738cells for the subsequent panning,whereas the unbound phages were removed by washing with *** concentrations of coating antigen were decreased(83.3,62.5,and 41.7μg/mL),whereas the Tween-20 concentration in the TBST was increased from 0.1%to 0.5%(v/v)in linear *** output/input ratio of phages after each round of panning was used to determine the enrichment efficiency,which increased from 5.95×10to 5.10×*** three rounds of panning,the titer of phages recovered from recombinant LILRB2-Fc were significantly increased by approximately 856.4 fol

关键词： LILRB2 central nervous system phage display targeting peptide

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A composite peptide-supramolecular microneedle system for melanoma immunotherapy

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Nano Research 2023年第4期16卷 5335-5345页

作者： Mengzhen Li Minxuan Wang Lingyun Li Limin Zhang Bing Ma Weizhi Wang Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information TechnologyKey Laboratory of Cluster Science of Ministry of EducationBeijing Key Laboratory of Photoelectronic/Electro-photonic Conversion MaterialsSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081China

Despite recent advances in melanoma treatment through the use of antibody immunotherapy,the clinical benefit remains restricted by its inefficient infiltration and immunosuppression within the tumor microenvironment(TME).In addition,immunerelated adverse events(irAEs)have often occurred due to the off-target binding of therapeutic drugs to normal tissues after systematic ***,we constructed an integrated and cascaded drug delivery system for the treatment of *** addition to blocking the programmed cell death protein 1 or its ligand(PD-1/PD-L1)axis,the PD-L1 targeting peptide(FE)with spherical micelle self-assembly characteristics could also effectively encapsulate the immune adjuvant resiquimod(R848),and form a complete nano ***^(R)was further integrated into tumor-responsive microneedles(MNs)to establish FE^(R)@MN and could reach the cascaded ***^(R)could be sustainedly released from the MN system and disassemble into monomers,achieving PD-1/PD-L1 axis blockade whilst reprogramming the immunosuppressive ***,FE^(R)@MN permits the controllable release and retention enhancement of the targeting peptide in the TME,thus causing prolonged PD-L1 blockade *** is demonstrated that this synergistic treatment could efficiently inhibit melanoma growth,providing a new strategy for the combination treatment of melanoma.

关键词： targeting peptide cascaded drug delivery microneedle immune checkpoint blockade self-assembly

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Converting antimicrobial into targeting peptides reveals key features governing protein import into mitochondria and chloroplasts

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Plant Communications 2023年第4期4卷 99-116页

作者： Oliver D.Caspari Clotilde Garrido Chris OLaw Yves Choquet Francis-Andre´Wollman Ingrid Lafontaine UMR7141(CNRS/Sorbonne Universite´) Institut de Biologie Physico-Chimique13 Rue Pierre et Marie Curie75005 ParisFrance Centre for Microscopy and Cellular Imaging Biology Department Loyola Campus of Concordia University7141 Sherbrooke W.Montre´alQC H4B 1R6Canada Present address:Department of Microbiology Institut Pasteur28 Rue Docteur Roux75015 ParisFrance Present address:UMR7238(CNRS/Sorbonne Universite´) Institut de Biologie Paris-SeineSorbonne Jussieu 7-9 quai Saint Bernard75005 ParisFrance

We asked what peptide features govern targeting to the mitochondria versus the chloroplast,using antimicrobial peptides as a starting *** approach was inspired by the endosymbiotic hypothesis that organelle-targeting peptides derive from antimicrobial amphipathic peptides delivered by the host cell,to which organelle progenitors became *** explore the molecular changes required to convert antimicrobial into targeting peptides,we expressed a set of 13 antimicrobial peptides in Chlamydomonas *** were systematically modified to test distinctive features of mitochondrion-and chloroplast-targeting peptides,and we assessed their targeting potential by following the intracellular localization and maturation of a Venus fluorescent reporter used as a cargo *** targeting can be achieved by some unmodified antimicrobial peptide *** to both organelles is improved by replacing lysines with *** targeting is enabled by the presence of flanking unstructured sequences,additional constraints consistent with chloroplast endosymbiosis having occurred in a cell that already contained *** indeed targeting peptides evolved from antimicrobial peptides,then required modifications imply a temporal evolutionary scenario with an early exchange of cationic residues and a late acquisition of chloroplast-specific motifs.

关键词： antimicrobial peptide Chlamydomonas reinhardtii endosymbiotic organellogenesis presequence targeting peptide transit peptide

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Ultra-small superparamagnetic iron oxide nanoparticles for intra-articular targeting of cartilage in early osteoarthritis

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Regenerative Biomaterials 2023年第1期10卷 1111-1121页

作者： Jun Wu Changqiang Wu Zhongyuan Cai Haojie Gu Li Liu Chunchao Xia Su Lui Qiyong Gong Bin Song Hua Ai Institute for Disaster Management and Reconstruction Sichuan UniversityChengdu 610207China Medical Imaging Key Laboratory of Sichuan Province School of Medical ImagingNorth Sichuan Medical CollegeNanchong 637000China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China Department of Radiology West China HospitalSichuan UniversityChengdu 610041China Department of Radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province Key Laboratory of Transplant Engineering and ImmunologyNHCResearch Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610064China Department of Radiology West China Xiamen Hospital of Sichuan UniversityFujianXiamen 361000China Department of Radiology Sanya People’s HospitalHainanSanya 572000China

Early diagnosis of osteoarthritis(OA)is critical for effective cartilage ***,lack of blood vessels in articular cartilage poses a barrier to contrast agent delivery and subsequent diagnostic *** address this challenge,we proposed to develop ultra-small superparamagnetic iron oxide nanoparticles(SPIONs,4 nm)that can penetrate into the matrix of articular cartilage,and further modified with the peptide ligand WYRGRL(particle size,5.9 nm),which allows SPIONs to bind to type II collagen in the cartilage matrix and increase the retention of *** II collagen in the cartilage matrix is gradually lost with the progression of OA,consequently,the binding of peptide-modified ultra-small SPIONs to type II collagen in the OA cartilage matrix is less,thus presenting different magnetic resonance(MR)signals in OA group from the normal *** introducing the AND logical operation,damaged cartilage can be differentiated from the surrounding normal tissue on T1 and T2 AND logical map of MR images,and this was also verified in histology ***,this work provides an effective strategy for delivering nanosized imaging agents to articular cartilage,which could potentially be used to diagnosis joint-related diseases such as osteoarthritis.

关键词： early osteoarthritis magnetic resonance imaging superparamagnetic iron oxide collagen type II targeting peptide

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