Publications by authors named "Zhichu Xiang"

9 Publications

  • Page 1 of 1

CD151 enrichment in exosomes of luminal androgen receptor breast cancer cell line contributes to cell invasion.

Biochimie 2021 Jun 23;189:65-75. Epub 2021 Jun 23.

Laboratory of Theoretical and Computational Nanoscience, CAS Key Laboratory of Nanophotonic Materials and Devices, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Ambient Particles Health Effects and Prevention Techniques, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100190, PR China. Electronic address:

Breast cancer is the most common and highly heterogeneous disease in women worldwide. Given the challenges in the treatment of advanced metastatic breast cancer, it is necessary to understand the molecular mechanisms related to disease progression. Exosomes play various roles in the progression of tumors, including promoting the invasion and advancing the distant metastasis. To study the molecular mechanisms related to the progression of luminal androgen receptor (LAR) breast cancer, we first isolated exosomes of MDA-MB-453 cells, a representative cell line of LAR. Through quantitative proteomic analysis, we identified 180 proteins specifically enriched in exosomes after comparing with those in cells, microvesicles, and the 150K supernatant. Among these, CD151, a protein involved in the regulation of cell motility was the most enriched one. CD151-knockdown exosomes reduced the invasion ability of the recipient breast cancer cell and lowered the phosphorylation level of tyrosine-protein kinase Lck, indicating that the invasion of LAR breast cancer may be due to CD151-enriched exosomes. Our work reports for the first time that CD151 was highly abundant in the exosomes of MDA-MB-453 cells and expands the understanding of the development process of LAR subtype, suggesting CD151 may be a potential candidate for the treatment of LAR breast cancer.
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http://dx.doi.org/10.1016/j.biochi.2021.06.007DOI Listing
June 2021

Drug-internalized bacterial swimmers for magnetically manipulable tumor-targeted drug delivery.

Nanoscale 2020 Jul;12(25):13513-13522

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China. and Laboratory of Theoretical and Computational Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China and University of Chinese Academy of Sciences, Beijing 100049, China and Sino-Danish Center for Education and Research, Beijing 101408, China and Beijing Key Laboratory of Ambient Particles Health Effects and Prevention Techniques, National Center for Nanoscience and Technology, Beijing 100190, China.

Tumor-targeted drug carriers are becoming attractive for precise drug delivery in anti-tumor therapy. However, a lot of the reported drug delivery systems are complicatedly designed and their destiny in vivo is beyond our control, which limited their clinical applications. Hence, it is urgently needed to develop spatio-manipulable self-propelled nanosystems for drug delivery in a facile way. Here, we have successfully constructed drug-internalized bacterial swimmers, whose movement can be manually controlled by an external magnetic field (MF). We demonstrate that the swimmers maintain the mobility to align and swim along MF lines. Further studies reveal that the doxorubicin (DOX-) internalized bacterial swimmers are able to navigate toward tumor sites under the guidance of MF, rendering enhanced anti-tumor efficacy compared with that of dead ones and free DOX. Therefore, the MF-guided bacterial swimmers hold great promise for spatio-manipulable drug delivery in precision medicine.
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http://dx.doi.org/10.1039/d0nr01892aDOI Listing
July 2020

A Protein Corona Adsorbed to a Bacterial Magnetosome Affects Its Cellular Uptake.

Int J Nanomedicine 2020 6;15:1481-1498. Epub 2020 Mar 6.

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

Purpose: It is well known that when exposed to human blood plasma, nanoparticles are predominantly coated by a layer of proteins, forming a corona that will mediate the subsequent cell interactions. Magnetosomes are protein-rich membrane nanoparticles which are synthesized by magnetic bacteria; these have gained a lot of attention owing to their unique magnetic and biochemical characteristics. Nevertheless, whether bacterial magnetosomes have a corona after interacting with the plasma, and how such a corona affects nanoparticle-cell interactions is yet to be elucidated. The aim of this study was to characterize corona formation around a bacterial magnetosome and to assess the functional consequences.

Methods: Magnetosomes were isolated from the magnetotactic bacteria, (MSR-1). Size, morphology, and zeta potential were measured by transmission electron microscopy and dynamic light scattering. A quantitative characterization of plasma corona proteins was performed using LC-MS/MS. Protein absorption was further examined by circular dichroism and the effect of the corona on cellular uptake was investigated by microscopy and spectroscopy.

Results: Various serum proteins were found to be selectively adsorbed on the surface of the bacterial magnetosomes following plasma exposure, forming a corona. Compared to the pristine magnetosomes, the acquired corona promoted efficient cellular uptake by human vascular endothelial cells. Using a protein-interaction prediction method, we identified cell surface receptors that could potentially associate with abundant corona components. Of these, one abundant corona protein, ApoE, may be responsible for internalization of the magnetosome-corona complex through LDL receptor-mediated internalization.

Conclusion: Our findings provide clues as to the physiological response to magnetosomes and also reveal the corona composition of this membrane-coated nanomaterial after exposure to blood plasma.
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http://dx.doi.org/10.2147/IJN.S220082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065717PMC
May 2020

Peptosome Coadministration Improves Nanoparticle Delivery to Tumors through NRP1-Mediated Co-Endocytosis.

Biomolecules 2019 05 5;9(5). Epub 2019 May 5.

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

Improving the efficacy of nanoparticles (NPs) delivery to tumors is critical for cancer diagnosis and therapy. In our previous work, amphiphilic peptide APPA self-assembled nanocarriers were designed and constructed for cargo delivery to tumors with high efficiency. In this study, we explore the use of APPA self-assembled peptosomes as a nanoparticle adjuvant to enhance the delivery of nanoparticles and antibodies to integrin αvβ3 and neuropilin-1 (NRP1) positive tumors. The enhanced tumor delivery of coadministered NPs was confirmed by better magnetosome (Mag)-based T-weighted magnetic resonance imaging (MRI), liposome-based fluorescence imaging, as well as the improved anti-tumor efficacy of monoclonal antibodies (trastuzumab in this case) and doxorubicin (DOX)-containing liposomes. Interestingly, the improvement is most significant for the delivering of compounds that have active or passive tumor targeting ability, such as antibodies or NPs that have enhanced permeability and retention (EPR) effect. However, for non-targeting small molecules, the effect is not significant. In vitro and in vivo studies suggest that both peptosomes and the coadministered compounds might be internalized into cells through a NRP1 mediated co-endocytosis (CoE) pathway. The improved delivery of coadministered NPs and antibodies to tumors suggests that the coadministration with APPA self-assembled peptosomes could be a valuable approach for advancing αvβ3 and NRP1 positive tumors diagnosis and therapy.
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http://dx.doi.org/10.3390/biom9050172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572427PMC
May 2019

Proteomic profiling of RAW264.7 macrophage cells exposed to graphene oxide: insights into acute cellular responses.

Nanotoxicology 2019 02 17;13(1):35-49. Epub 2019 Jan 17.

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

Although the toxicity and molecular mechanisms of graphene oxide (GO) have been reported for several cell types, no proteomic study of GO has yet been conducted on macrophage cells. In this study, we used proteomics based on stable isotope labeling with amino acids in cell culture (SILAC) to quantify the proteomic changes in macrophage RAW 264.7 cells following GO treatment. We found 73 proteins that were significantly dysregulated after GO treatment. The down-regulated proteins included many ribosomal subunit proteins, indicating that GO affected cell growth. The most elevated proteins were lipoprotein lipase (LPL) and lysozyme 1 (LYZ1) which have not been reported before, and both can be used as candidate markers for GO exposure. Further enrichment analysis of the up-regulated proteins indicated these proteins are associated with the integrin complex and membrane rafts, as well as with two signal pathways: the phagosome and steroid biosynthesis pathways. We confirmed a GO concentration-dependent increase in membrane rafts and the production of phagosomes. GO exposure also induced necrotic cell death and an inflammation response in RAW 264.7 cells. We also observed an increase in the oxidative stress response (ROS) and autophagy, and the results suggest that ROS induced autophagy by the ROS-NRF2-P62 pathway.
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http://dx.doi.org/10.1080/17435390.2018.1530389DOI Listing
February 2019

Peptide probes derived from pertuzumab by molecular dynamics modeling for HER2 positive tumor imaging.

PLoS Comput Biol 2017 Apr 13;13(4):e1005441. Epub 2017 Apr 13.

CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing, China.

A high level of HER2 expression in breast cancer correlates with a higher tumor growth rate, high metastatic potential, and a poor long-term patient survival rate. Pertuzumab, a human monoclonal antibody, can reduce the effect of HER2 overexpression by preventing HER2 dimerization. In this study, a combination protocol of molecular dynamics modeling and MM/GBSA binding free energy calculations was applied to design peptides that interact with HER2 based on the HER2/pertuzumab crystal structure. Based on a β hairpin in pertuzumab from Glu46 to Lys65-which plays a key role in interacting with HER2-mutations were carried out in silico to improve the binding free energy of the hairpin that interacts with the Phe256-Lys314 of the HER2 protein. Combined the use of one-bead-one-compound library screening, among all the mutations, a peptide (58F63Y) with the lowest binding free energy was confirmed experimentally to have the highest affinity, and it may be used as a new probe in diagnosing and treating HER2-positive breast cancer.
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http://dx.doi.org/10.1371/journal.pcbi.1005441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390981PMC
April 2017

Tumor detection using magnetosome nanoparticles functionalized with a newly screened EGFR/HER2 targeting peptide.

Biomaterials 2017 01 16;115:53-64. Epub 2016 Nov 16.

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

A novel peptide (P75) targeting EGFR and HER2 is successfully screened from a one-bead-one-compound (OBOC) library containing approximately 2 × 10 peptides built with the aid of computational simulation. In vitro and in vivo analyses show that P75 binds to human epithelial growth factor receptor (EGFR) with nanomolar affinity and to epithelial growth factor receptor-2 (HER2) with a lower affinity but comparable to other reported peptides. The peptide is used to modify the surface of magnetosome nanoparticles (NPs) for targeted magnetic resonance imaging (MRI). In vitro and in vivo fluorescence imaging results suggest peptide P75 modified magnetosomes (Mag-P75) specifically bind to MDA-MB-468 and SKBR3 cells as well as xenograft tumors with surprisingly low accumulation in other organs including liver and kidney. In vivo T-weighted MR imaging studies of the xenograft tumors from SKBR3 and MDA-MB-468 cells show obviously negative contrast enhancement. The high affinity and specificity of P75 to EGFR and HER2 positive tumors, together with the success of peptide functionalized magnetosome NPs for targeted MRI demonstrate the potential of this peptide being used in the EGFR and HER2 positive tumors diagnosis and therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2016.11.022DOI Listing
January 2017

HER2 Targeting Peptides Screening and Applications in Tumor Imaging and Drug Delivery.

Theranostics 2016 28;6(8):1261-73. Epub 2016 May 28.

1. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China;; 2. CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China;

Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery.
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http://dx.doi.org/10.7150/thno.14302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893650PMC
October 2017

Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors.

Theranostics 2015 1;5(10):1154-65. Epub 2015 Aug 1.

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

To identify peptides with high affinity and specificity against human epidermal growth factor receptor 2 (HER2), a series of peptides were designed based on the structure of HER2 and its Z(HER2:342) affibody. By using a combination protocol of molecular dynamics modeling, MM/GBSA binding free energy calculations, and binding free energy decomposition analysis, two novel peptides with 27 residues, pep27 and pep27-24M, were successfully obtained. Immunocytochemistry and flow cytometry analysis verified that both peptides can specifically bind to the extracellular domain of HER2 protein at cellular level. The Surface Plasmon Resonance imaging (SPRi) analysis showed that dissociation constants (K D) of these two peptides were around 300 nmol/L. Furthermore, fluorescence imaging of peptides against nude mice xenografted with SKBR3 cells indicated that both peptides have strong affinity and high specificity to HER2 positive tumors.
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http://dx.doi.org/10.7150/thno.12398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533098PMC
April 2016
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