Publications by authors named "Xiangli Bu"

15 Publications

  • Page 1 of 1

Wireless Wearable Ultrasound Sensor on a Paper Substrate to Characterize Respiratory Behavior.

ACS Sens 2019 04 20;4(4):944-952. Epub 2019 Mar 20.

School of Electrical, Computer, and Energy Engineering , Arizona State University , Tempe , Arizona 85281 , United States.

Respiratory behavior contains crucial parameters to feature lung functionality, including respiratory rate, profile, and volume. The current well-adopted method to characterize respiratory behavior is spirometry using a spirometer, which is bulky, heavy, expensive, requires a trained provider to operate, and is incapable of continuous monitoring of respiratory behavior, which is often critical to assess chronic respiratory diseases. This work presents a wireless wearable sensor on a paper substrate that is capable of continuous monitoring of respiratory behavior and delivering the clinically relevant respiratory information to a smartphone. The wireless wearable sensor was attached on the midway of the xiphoid process and the costal margin, corresponding to the abdomen-apposed rib cage, based on the anatomical and experimental analysis. The sensor, with a footprint of 40 × 35 × 6 mm and weighing 6.5 g, including a 2.7 g battery, consists of three subsystems, (i) ultrasound emitter, (ii) ultrasound receiver, and (iii) data acquisition and wireless transmitter. The sensor converts the linear strain at the wearing site to the lung volume change by measuring the change in ultrasound pressure as a function of the distance between the emitter and the receiver. The temporal lung volume change data, directly converted from the ultrasound pressure, is wirelessly transmitted to a smartphone where a custom-designed app computes to show volume-time and flow rate-volume loop graphs, standard respiratory analysis plots. The app analyzes the plots to show the clinically relevant respiratory behavioral parameters, such as forced vital capacity (FVC) and forced expiratory volume delivered in the first second (FEV). Potential user-induced error on sensor placement and temperature sensitivity were studied to demonstrate the sensor maintains its performance within a reasonable range of those variables. Eight volunteers were recruited to evaluate the sensor, which showed the mean deviation of the FEV/FVC ratio in the range of 0.00-4.25% when benchmarked by the spirometer. The continuous measurement of respiratory behavioral parameters helps track the progression of the respiratory diseases, including asthma progression to provide alerts to relevant caregivers to seek needed timely treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssensors.9b00043DOI Listing
April 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.14302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893650PMC
October 2017

Discovering of Tumor-targeting Peptides using Bi-functional Microarray.

Adv Healthc Mater 2015 Dec 9;4(18):2802-8. Epub 2015 Nov 9.

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

A bi-functional microarray for in situ peptide screening is presented herein, from which an affinity peptide towards EpCAM is screened out for tumor cell capture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.201500724DOI Listing
December 2015

Quantitative Proteomic Analysis of Cellular Resistance to the Nanoparticle Abraxane.

ACS Nano 2015 Oct 9;9(10):10099-112. Epub 2015 Sep 9.

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

Abraxane, an FDA-approved albumin-bound nanoparticle (NP) form of paclitaxel (PTX) to treat breast cancer and nonsmall cell lung cancer (NSCLC), has been demonstrated to be more effective than the original Taxol, the single molecule form. We have established a cell line from NSCLC A549 cells to be resistant to Abraxane. To further understand the molecular mechanisms involved in the NP drug resistance, global protein expression profiles of Abraxane sensitive (A549) and resistant cells (A549/Abr), along with the treatment of Abraxane, have been obtained by a quantitative proteomic approach. The most significantly differentially expressed proteins are associated with lipid metabolism, cell cycle, cytoskeleton, apoptosis pathways and processes, suggesting several mechanisms are working synergistically in A549 Abraxane-resistant cells. Overexpression of proteins in the lipid metabolism processes, such as E3 ubiquitin-protein ligase RNF139 (RNF139) and Hydroxymethylglutaryl-CoA synthase (HMGCS1), have not been reported previously in the study of paclitaxel resistance, suggesting possibly different mechanism between nanoparticle and single molecular drug resistance. In particular, RNF139 is one of the most up-regulated proteins in A549 Abraxane-resistant cell line, but remains no change when the resistant cells were further treated with Abraxane and down-regulated in the sensitive cells after 4 h treatment of Abraxane. This study shows the use of a proteomic strategy to understand the unique response of drug resistant cells to a nanoparticle therapeutic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.5b03677DOI Listing
October 2015

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.12398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533098PMC
April 2016

Microarray based screening of peptide nano probes for HER2 positive tumor.

Anal Chem 2015 Aug 6;87(16):8367-72. Epub 2015 Aug 6.

§Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, United States.

Peptides are excellent biointerface molecules and diagnostic probes with many advantages such as good penetration, short turnover time, and low cost. We report here an efficient peptide screening strategy based on in situ single bead sequencing on a microarray. Two novel peptides YLFFVFER (H6) and KLRLEWNR (H10) specifically binding to the tumor biomarker human epidermal growth factor receptor 2 (HER2) with aKD of 10(-8) M were obtained from a 10(5) library. Conjugated to nanoparticles, both the H6 and H10 probes showed specific accumulation in HER2-positive tumor tissues in xenografted mice by in vivo imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.5b01588DOI Listing
August 2015

Abraxane, the Nanoparticle Formulation of Paclitaxel Can Induce Drug Resistance by Up-Regulation of P-gp.

PLoS One 2015 16;10(7):e0131429. Epub 2015 Jul 16.

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

P-glycoprotein (P-gp) can actively pump paclitaxel (PTX) out of cells and induces drug resistance. Abraxane, a nanoparticle (NP) formulation of PTX, has multiple clinical advantages over the single molecule form. However, it is still unclear whether Abraxane overcomes the common small molecule drug resistance problem mediated by P-gp. Here we were able to establish an Abraxane-resistant cell line from the lung adenocarcinoma cell line A549. We compared the transcriptome of A549/Abr resistant cell line to that of its parental cell line using RNA-Seq technology. Several pathways were found to be up or down regulated. Specifically, the most significantly up-regulated gene was ABCB1, which translates into P-glycoprotein. We verified the overexpression of P-glycoprotein and confirmed its function by reversing the drug resistance with P-gp inhibitor Verapamil. The results suggest that efflux pathway plays an important role in the Abraxane-resistant cell line we established. However, the relevance of this P-gp mediated Abraxane resistance in tumors of lung cancer patients remains unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131429PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504487PMC
April 2016

Label-free detection microarray for novel peptide ligands screening base on MS-SPRi combination.

Talanta 2015 Mar 18;134:705-711. Epub 2014 Dec 18.

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China; Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; Institute for Systems Biology, 401 Terry Avenue N, Seattle, WA 98109, USA. Electronic address:

Peptides ligands with high affinity and high specificity towards specific targets is catching a good deal of interests in biomedical field. Traditional peptide screening procedure involves selection, sequencing and characterization and each step is time-consuming and labor-intensive. The combination between different analytical methods could provide an integrated plan for efficient peptide screening. We report herein a label-free detection microarray system to facilitate the whole one-bead-one-compound (OBOC) peptide screening process. A microwell array chip with two identical units can trap the candidate peptide beads in one-well-one-bead manner. Peptides on beads were photo-released in situ in the well and partly transferred to two identical chips for Surface Plasmon Resonance imaging (SPRi), and peptide left in the bi-unit microwell array chip was remain for in situ single bead sequencing by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Using the bi-unit imprinted chip system, affinity peptides towards AD protein were efficiently screened out both qualitatively and quantitatively from 10(4) candidates. The method provides a universal solution for high efficiency and high throughput ligands screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2014.12.012DOI Listing
March 2015

Label-free detection of Alzheimer's disease through the ADP3 peptoid recognizing the serum amyloid-beta42 peptide.

Chem Commun (Camb) 2015 Jan;51(4):718-21

National Center for Nanoscience and Technology, No. 11, Beiyitiao Zhongguancun, Beijing, 100190, P.R. China.

The early diagnosis of Alzheimer's disease (AD) is challenging due to the lack of reliable methods for detecting its biomarkers in the noninvasive biopsies. We used surface plasmon resonance imaging to identify AD based on the detection of amyloid-beta42 in the serum by the ADP3 peptoid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c4cc07037bDOI Listing
January 2015

Rapid screening of peptide probes through in situ single-bead sequencing microarray.

Anal Chem 2014 Dec 14;86(23):11854-9. Epub 2014 Nov 14.

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

Peptide ligands as targeting probes for in vivo imaging and drug delivery have attracted great interest in the biomedical community. However, high affinity and specificity screening of large peptide libraries remains a tedious process. Here, we report a continuous-flow microfluidic method for one-bead-one-compound (OBOC) combinatorial peptide library screening. We screened a library with 2 × 10(5) peptide beads within 4 h and discovered 140 noncanonical peptide hits targeting the tumor marker, aminopeptidase N (APN). Using the Clustal algorithm, we identified the conserved sequence Tyr-XX-Tyr in the N terminal. We demonstrated that the novel sequence YVEYHLC peptides have both nanomolar affinity and high specificity for APN in ex vivo and in vivo models. We envision that the successful demonstration of this integrated novel nanotechnology for peptide screening and identification open a new avenue for rapid discovery of new peptide-based reagents for disease diagnostics and therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/ac503454zDOI Listing
December 2014

A flexible microneedle array as low-voltage electroporation electrodes for in vivo DNA and siRNA delivery.

Lab Chip 2014 Oct;14(20):4093-102

National Center for Nanoscience and Technology, Beijing 100190, China.

In vivo electroporation is an appealing method to deliver nucleic acid into living tissues, but the clinical application of such a method was limited due to severe tissue damage and poor coverage of the tissue surface. Here we present the validation of a novel flexible microneedle array electrode (MNAE) chip, in which the microneedle array and the flexible substrate are integrated together to simultaneously facilitate low-voltage electroporation and accomplish good coverage of the tissue surface. The efficient delivery of both DNA and siRNA was demonstrated on mice. Upon penetrating the high-resistance stratum corneum, the electroporation voltage was reduced to about 35 V, which was generally recognized safe for humans. Also, a pathological analysis of the microneedle-electroporated tissues was carried out to thoroughly assess the skin damage, which is an important consideration in pre-clinical studies of electroporation devices. This MNAE constitutes a novel way of in vivo delivery of siRNA and DNA to certain tissues or organs with satisfactory efficiency and good adaptation to the tissue surface profile as well as minimum tissue damage, thus avoiding the disadvantages of existing electroporation methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c4lc00800fDOI Listing
October 2014

Betaine homocysteine methyltransferase (BHMT) as a specific and sensitive blood marker for acute liver injury.

Biomarkers 2014 Nov 21;19(7):578-84. Epub 2014 Aug 21.

National Center for Nanoscience and Technology , Beijing , P.R. China .

We developed a high-performance ELISA assay and measured serum BHMT levels in healthy individuals and patients with acute liver injury (ALI). The detection range of this ELISA assay was from 1.56 to 100 ng/ml. BHMT levels are significantly higher in ALI groups. In the healthy group (n = 244), the median value (interquartile range, IQR 0-56.40) was 1.83 ng/ml. In the ALI group (n = 42), the median value of BHMT was 748.48 ng/ml (IQR, 0-51095.92). ROC curve analysis demonstrated good sensitivity (0.86) and specificity (0.98). In addition, in five ALI cases with time course samples available, BHMT and ALT both followed the "rise and fall" temporal pattern with the disease progression. However, the slopes of BHMT curves were steeper than ALT curves. And in three out of the five cases, BHMT levels peaked 1 day earlier than ALT levels be a sensitive marker with good prognostic value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/1354750X.2014.951880DOI Listing
November 2014

Label-free quantitative detection of tumor-derived exosomes through surface plasmon resonance imaging.

Anal Chem 2014 Sep 11;86(17):8857-64. Epub 2014 Aug 11.

National Center for Nanoscience and Technology , No. 11, Beiyitiao Zhongguancun, Beijing 100190, P. R. China.

Exosomes are endosome-derived membrane vesicles carrying proteins and nucleic acids that are involved in cellular functions such as intercellular communication, protein and RNA secretion, and antigen presentation. Therefore, exosomes serve as potential biomarkers for many diseases including cancer. Because exosomes are difficult to enrich or purify from biofluids, quantification of exosomes is tedious and inaccurate. Here, we present a real-time, label-free, and quantitative method to detect and characterize tumor-derived exosomes without enrichment or purification. Utilizing surface plasmon resonance imaging (SPRi) in combination with antibody microarrays specific to the extracellular domains of exosome membrane proteins, exosomes in tumor cell culture medium can be quantitatively detected. We found a positive correlation between the metastatic potential of tumor cell lines and exosome secretion. This method provides an easy, efficient, and novel way to detect exosome secretion and thus an avenue toward the diagnosis and prognosis prediction of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/ac5023056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151789PMC
September 2014

Bimodal imprint chips for peptide screening: integration of high-throughput sequencing by MS and affinity analyses by surface plasmon resonance imaging.

Anal Chem 2014 Apr 24;86(8):3703-7. Epub 2014 Mar 24.

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

Peptide probes and drugs have widespread applications in disease diagnostics and therapy. The demand for peptides ligands with high affinity and high specificity toward various targets has surged in the biomedical field in recent years. The traditional peptide screening procedure involves selection, sequencing, and characterization steps, and each step is manual and tedious. Herein, we developed a bimodal imprint microarray system to embrace the whole peptide screening process. Silver-sputtered silicon chip fabricated with microwell array can trap and pattern the candidate peptide beads in a one-well-one-bead manner. Peptides on beads were photocleaved in situ. A portion of the peptide in each well was transferred to a gold-coated chip to print the peptide array for high-throughput affinity analyses by surface plasmon resonance imaging (SPRi), and the peptide left in the silver-sputtered chip was ready for in situ single bead sequencing by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Using the bimodal imprint chip system, affinity peptides toward AHA were efficiently screened out from the 7 × 10(4) peptide library. The method provides a solution for high efficiency peptide screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/ac500465eDOI Listing
April 2014

Quantitative liver-specific protein fingerprint in blood: a signature for hepatotoxicity.

Theranostics 2014 14;4(2):215-28. Epub 2014 Jan 14.

2. Institute for Systems Biology, 401 Terry Avenue N, Seattle, Washington 98109, USA.

We discuss here a new approach to detecting hepatotoxicity by employing concentration changes of liver-specific blood proteins during disease progression. These proteins are capable of assessing the behaviors of their cognate liver biological networks for toxicity or disease perturbations. Blood biomarkers are highly desirable diagnostics as blood is easily accessible and baths virtually all organs. Fifteen liver-specific blood proteins were identified as markers of acetaminophen (APAP)-induced hepatotoxicity using three proteomic technologies: label-free antibody microarrays, quantitative immunoblotting, and targeted iTRAQ mass spectrometry. Liver-specific blood proteins produced a toxicity signature of eleven elevated and four attenuated blood protein levels. These blood protein perturbations begin to provide a systems view of key mechanistic features of APAP-induced liver injury relating to glutathione and S-adenosyl-L-methionine (SAMe) depletion, mitochondrial dysfunction, and liver responses to the stress. Two markers, elevated membrane-bound catechol-O-methyltransferase (MB-COMT) and attenuated retinol binding protein 4 (RBP4), report hepatic injury significantly earlier than the current gold standard liver biomarker, alanine transaminase (ALT). These biomarkers were perturbed prior to onset of irreversible liver injury. Ideal markers should be applicable for both rodent model studies and human clinical trials. Five of these mouse liver-specific blood markers had human orthologs that were also found to be responsive to human hepatotoxicity. This panel of liver-specific proteins has the potential to effectively identify the early toxicity onset, the nature and extent of liver injury and report on some of the APAP-perturbed liver networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.7868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900804PMC
September 2014
-->