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Towards the clinical translation of quantum dots: current preclinical barriers and future strategies

Historically, quantum dots (QDs) have generated tremendous excitement as a contrast agent, diagnostic tool, and even as a therapeutic in the 40 years since their discovery. Their brightness, narrow and tunable emission peaks, and large surface area for functionalization are all ideal properties for biomedical applications. However, there still are no clinically approved therapies utilizing QDs, and the toxicity of these systems have turned much of the excitement to disillusionment.
In this thesis work, I outline some of the key barriers that have prevented QD translation to clinical settings — namely, proper toxicology assessment and bioaccumulation — and demonstrate some potential strategies to overcome these barriers. In the first aim, I show that copper indium sulfide (CIS, CuInS2) QDs are actually toxic, in contrast to previous literature that assumed non-toxicity. This result emphasizes how toxicity evaluation must be done carefully with proper separation of QD components (core, shell, and surface coating) that can influence or confound results. I also show that the toxicity of CIS QDs was linked to their degradation in vitro, highlighting the second barrier.
In the second aim, I describe a novel, controlled synthesis of bornite (CuxFeS4) nanocrystals (NCs) with various Cu:Fe ratios and sizes and explore how those variables influence the optical properties of bornite. I also show the mechanism for the development of a localized surface plasmon resonance (LSRP) peak in bornite during oxidation, linking it to iron expulsion from the NCs and a subsequent rise in excess hole carriers.
Finally, in my third aim I look at how copper iron sulfides are biodegradable, non-toxic, and useful for photothermal treatment. I demonstrate this premise through the selective lysis of bacterial cells using a NC-peptide platform that couples the targeting power of antimicrobial peptides with the photothermal capacity of bornite NCs.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43713
Date26 January 2022
CreatorsKays, Joshua Christian
ContributorsDennis, Allison
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation
RightsAttribution-NonCommercial-ShareAlike 4.0 International, http://creativecommons.org/licenses/by-nc-sa/4.0/

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