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Characterizing the Role of Nanoparti...

Albanese, Alexandre.

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Characterizing the Role of Nanoparticle Design on Tumor Transport and Stability in the Extracellular Environment.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Characterizing the Role of Nanoparticle Design on Tumor Transport and Stability in the Extracellular Environment./
作者:	Albanese, Alexandre.
面頁冊數:	180 p.
附註:	Source: Dissertation Abstracts International, Volume: 75-11(E), Section: B.
Contained By:	Dissertation Abstracts International75-11B(E).
標題:	Engineering, Biomedical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3630480
ISBN:	9781321084566

Characterizing the Role of Nanoparticle Design on Tumor Transport and Stability in the Extracellular Environment.
Albanese, Alexandre.

Characterizing the Role of Nanoparticle Design on Tumor Transport and Stability in the Extracellular Environment. - 180 p.

Source: Dissertation Abstracts International, Volume: 75-11(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2014.

Nanotechnology has emerged as an exciting strategy for the delivery of diagnostic and therapeutic agents into established tumors. Advancements in nanomaterial synthesis have generated an extensive number of nanoparticle designs made from different materials. Unfortunately, it remains impossible to predict a design's effectiveness for in vivo tumor accumulation. Little is known about how a nanoparticle's morphology and surface chemistry affect its interactions with cells and proteins inside the tumor tissue. This thesis focuses on the development of in vitro experimental tools to evaluate how nanoparticle design affects transport in a three-dimensional tumor tissue and stability in the tumor microenvironment. Nanoparticle transport was evaluated using a novel 'tumor-on-a-chip' system where multicellular tumor spheroids were immobilized in a microfluidic channel. This setup created a three-dimensional tumor environment displaying physiological cell density, extracellular matrix organization, and interstitial flow rates. The tumor-on-a-chip demonstrated that accumulation of nanoparticles was limited to diameters below 110 nm and was improved by receptor targeting. Nanoparticle stability in the tumor microenvironment was evaluated using media isolated from different tumor cell lines. Nanoparticle diameter and surface chemistry were important determinants of stability in cancer cell-conditioned media. Small nanoparticles with unstable surface chemistries adsorbed cellular proteins on their surface and were prone to aggregation. Nanoparticle aggregation altered cellular interactions leading to changes in cell uptake. Using a novel technique to generate different aggregate sizes possessing a uniform surface composition, it was determined that aggregation can change receptor affinity, cell internalization mechanisms and sub-cellular sequestration patterns. Data from this thesis characterize the behavior of nanoparticles within modeled tumor environments and provide some preliminary design guidelines for maximizing nanoparticle tumor accumulation. This work highlights the importance of characterizing nano-bio interactions for engineering successful nanomaterial-based delivery systems.

ISBN: 9781321084566Subjects--Topical Terms:

1017684
Engineering, Biomedical.

Characterizing the Role of Nanoparticle Design on Tumor Transport and Stability in the Extracellular Environment.
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