Scavenger Receptor Expression is Differentially Affected by DNAzyme-Gold Nanoparticle Conjugates in a Lung Model Pubblico

Abstract

Scavenger receptor (SR) surface proteins are highly conserved motifs and are implicated in the uptake of conjugated DNAzyme-nanoparticles (DzNP), a promising novel nanotherapy for lung diseases. The role of SRs in DzNP uptake in the lung is poorly understood, so we examined whether DzNP exposure and uptake regulates gene expression in murine alveolar macrophages and primary human airway epithelial cells. Gene expression is modulated by 2251DzNP in both MH-S cells and NhTE cells, suggesting that 2251DzNP may facilitate its own uptake, but the extent to which each SR is affected depends heavily on its class and involvement in inflammation signaling pathways. This represents novel findings in lung tissue that support previous work done on nanotherapy uptake and influences the development of novel therapies for lung diseases.

Table of Contents

List of Figures ............................................................................................................................................................. ii

List of Abbreviations ............................................................................................................................................... ii

I. Introduction ....................................................................................................................................................... 1

II. Materials and Methods .................................................................................................................................. 8

1.1. Materials ........................................................................................................................................................... 8

1.2. Gold nanoparticle synthesis .............................................................................................................................8

1.3. DNAzyme-gold nanoparticles functionalization ............................................................................................ 8

1.4. Cell culture ...................................................................................................................................................... 9

1.5. Particle uptake by macrophages ..................................................................................................................... 10

1.6. In vitro gene expression ................................................................................................................................. 11

1.7. Statistics ......................................................................................................................................................... 11

III. Results .......................................................................................................................................................... 12

1.1. MARCO and MSR1 Gene Expression with Dose Response to DSS and DzNP in MH-S Cells .......................... 12

1.2. MARCO and MSR1 Gene Expression for Concomitant 2251DzNP and low MW DSS in MH-S Cells .......... 14

1.3. Low Dose 2251DzNP Expression Levels in MH-S Cells: ..............................................................................16

1.4. MSR1 Expression in NhTE Cells with Concomitant Treatment ....................................................................17

1.5. CD36 and COLEC12 Expression in NhTE Cells with Concomitant Treatment ............................................... 18

1.6. MH-S Particle Uptake ...................................................................................................................................... 19

IV. Discussion ................................................................................................................................................... 20

V. References ....................................................................................................................................................... 24

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Chemistry, Biochemistry Biology, Molecular
Parola chiave	lung epithelial cells scavenger receptors nanoparticle uptake uptake mechanism alveolar macrophages gold nanoparticle DNAzyme
Committee Chair / Thesis Advisor	Dr. Cherry Wongtrakool, Emory University
Committee Members	Dr. Khalid Salaita, Emory University Dr. Jose Soria, Emory University

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