Ligand shell morphology of water-soluble mixed-monolayer protected gold nanoparticles

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2007.Includes bibliographical references (leaves 41-43).Nanoparticles comprise a versatile class of nanomaterials that consist of particles that have a characteristic length scale less than 100nm. They are on a similar length scale as many biological elements, so it is fitting that they are being used increasingly in biological systems for a variety of applications. Interesting properties of water-soluble metal nanoparticles that could lead to novel biological applications include bio-catalytic, sensing, and light scattering capabilities. We will present here the characterization of novel highly water-soluble gold nanoparticles that can be used as model systems to study the fundamental mechanisms of cellular uptake and intracellular trafficking.by Suelin Chen.S.M

Polymer-coated iron oxide nanoparticles for medical imaging

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 144-157).One of the most versatile and safe materials used in medicine are polymer-coated iron oxide nanoparticles. This dissertation describes several formulations for in vivo imaging applications. The paramagnetic polymer-coated iron oxide nanoparticle aminoSPARK is used as a fluorescence-mediated tomography (FMT) imaging agent for stratification of prostate cancer tumors. This is achieved by conjugating it to a peptide that targets SPARC (secreted protein acidic rich in cysteine), a biomarker protein associated with aggressive forms of prostate cancer. Several types of polymer coatings for iron oxide nanoparticles have been systematically explored using a novel high-throughput screening technique to optimize coating chemistries and synthetic conditions to produce nanoparticles with maximum stability and ability to lower T2 contrast for MR imaging (R2, or relaxivity). Carboxymethyl dextran emerged from the screen as an ideal coating for superparamagnetic iron oxide nanoparticles. A commercially available, FDA-approved nanoparticle with similar surface chemistry, Feraheme, was chosen as a platform nanoparticle for further development. This work presents the first instance of chemical modification of Feraheme, making it more amenable to bioconjugation by converting its free carboxyl groups to free amine groups. This amine-functionalized Feraheme nanoparticle (amino-FH) is then used as a base nanoparticle to which various targeting and reporting functionalities can be added. A FH-based nanoparticle that can be used for cell loading is synthesized by covalently combining Feraheme with protamine, a pharmaceutical that also acts as a membrane translocating agent. A rhodamine-protamine conjugate is synthesized and then covalently bound to amino-FH using carbodiimide (CDI) chemistry. This results in a magnetofluorescent cell-labeling nanoparticle (ProRho-FH) that is readily taken up by mouse mesenchymal stem cells and U87 glioma cells. ProRho-FH can be used to non-invasively track cells for development and monitoring of cell-based therapies or for further investigation of biological mechanisms such as cell migration, tumor growth, and metastasis. This combination of two FDA-approved, commercially available materials to yield a superparamagnetic and fluorescent cell labeling nanoparticle is an excellent alternative to the recently discontinued Feridex. All polymer-coated iron oxide nanoparticles used in this dissertation were thoroughly characterized to fully understand their physicochemical and magnetic properties.by Suelin Chen.Ph.D

Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

Nanoscale objects are typically internalized by cells into membrane-bounded endosomes and fail to access the cytosolic cell machinery. Whereas some biomacromolecules may penetrate or fuse with cell membranes without overt membrane disruption, no synthetic material of comparable size has shown this property yet. Cationic nano-objects pass through cell membranes by generating transient holes, a process associated with cytotoxicity. Studies aimed at generating cell-penetrating nanomaterials have focused on the effect of size, shape and composition. Here, we compare membrane penetration by two nanoparticle 'isomers' with similar composition (same hydrophobic content), one coated with subnanometre striations of alternating anionic and hydrophobic groups, and the other coated with the same moieties but in a random distribution. We show that the former particles penetrate the plasma membrane without bilayer disruption, whereas the latter are mostly trapped in endosomes. Our results offer a paradigm for analysing the fundamental problem of cell-membrane-penetrating bio- and macro-molecules

PDMS-based microfluidics for proteomic analysis.

A microfluidic poly(dimethylsiloxane) (PDMS) microdevice was realized, combining on-line protein electrophoretic separation, selection, and digestion of a protein of interest for identification by mass spectrometry. The system includes eight integrated valves and one micropump dedicated to control the flow operations. Myoglobin was successfully isolated from bovine serum albumin (BSA), then selected using integrated valves and digested in a rotary micromixer. Proteolytic peptides were recovered from the micromixer for protein identification. Total analysis from sample injection to protein identification is performed under 30 minutes, with samples of tens of nanolitres. The paper shows that PDMS technology can be successfully used for integrating complex preparation protocols of proteic samples prior to MS analysis

The revised Approved Instructional Resources score:An improved quality evaluation tool for online educational resources

BACKGROUND: Free Open-Access Medical education (FOAM) use among residents continues to rise. However, it often lacks quality assurance processes and residents receive little guidance on quality assessment. The Academic Life in Emergency Medicine Approved Instructional Resources tool (AAT) was created for FOAM appraisal by and for expert educators and has demonstrated validity in this context. It has yet to be evaluated in other populations.OBJECTIVES: We assessed the AAT's usability in a diverse population of practicing emergency medicine (EM) physicians, residents, and medical students; solicited feedback; and developed a revised tool.METHODS: As part of the Medical Education Translational Resources: Impact and Quality (METRIQ) study, we recruited medical students, EM residents, and EM attendings to evaluate five FOAM posts with the AAT and provide quantitative and qualitative feedback via an online survey. Two independent analysts performed a qualitative thematic analysis with discrepancies resolved through discussion and negotiated consensus. This analysis informed development of an initial revised AAT, which was then further refined after pilot testing among the author group. The final tool was reassessed for reliability.RESULTS: Of 330 recruited international participants, 309 completed all ratings. The Best Evidence in Emergency Medicine (BEEM) score was the component most frequently reported as difficult to use. Several themes emerged from the qualitative analysis: for ease of use-understandable, logically structured, concise, and aligned with educational value. Limitations include deviation from questionnaire best practices, validity concerns, and challenges assessing evidence-based medicine. Themes supporting its use include evaluative utility and usability. The author group pilot tested the initial revised AAT, revealing a total score average measure intraclass correlation coefficient (ICC) of moderate reliability (ICC = 0.68, 95% confidence interval [CI] = 0 to 0.962). The final AAT's average measure ICC was 0.88 (95% CI = 0.77 to 0.95).CONCLUSIONS: We developed the final revised AAT from usability feedback. The new score has significantly increased usability, but will need to be reassessed for reliability in a broad population.</p

The Social Media Index as an Indicator of Quality for Emergency Medicine Blogs: A METRIQ Study

Study objective: Online educational resources such as blogs are increasingly used for education by emergency medicine clinicians. The Social Media Index was developed to quantify their relative impact. The Medical Education Translational Resources: Indicators of Quality (METRIQ) study was conducted in part to determine the association between the Social Media Index score and quality as measured by gestalt and previously derived quality instruments. Methods: Ten blogs were randomly selected from a list of emergency medicine and critical care Web sites. The 2 most recent clinically oriented blog posts published on these blogs were evaluated with gestalt, the Academic Life in Emergency Medicine Approved Instructional Resources (ALiEM AIR) score, and the METRIQ-8 score. Volunteer raters (including medical students, emergency medicine residents, and emergency medicine attending physicians) were identified with a multimodal recruitment methodology. The Social Media Index was calculated in February 2016, November 2016, April 2017, and December 2017. Pearson's correlations were calculated between the Social Media Index and the average rater gestalt, ALiEM AIR score, and METRIQ-8 score. Results: A total of 309 of 330 raters completed all ratings (93.6%). The Social Media Index correlated moderately to strongly with the mean rater gestalt ratings (range 0.69 to 0.76) and moderately with the mean rater ALiEM AIR score (range 0.55 to 0.61) and METRIQ-8 score (range 0.53 to 0.57) during the month of the blog post's selection and for 2 years after. Conclusion: The Social Media Index's correlation with multiple quality evaluation instruments over time supports the hypothesis that it is associated with overall Web site quality. It can play a role in guiding individuals to high-quality resources that can be reviewed with critical appraisal techniques