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Study of Iron Oxide Magnetic Nanoparticles in Cancer Cell Destruction and Cell Separation

Zhao, Jiaqi (2019) Study of Iron Oxide Magnetic Nanoparticles in Cancer Cell Destruction and Cell Separation. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Due to their adjustable physiochemical properties and proven biocompatibility, iron oxide (Fe3O4) magnetic nanoparticles are promising in drug delivery, magnetic resonance imaging and catalysis. In this thesis, we have utilized two types of iron oxide nanoparticles: i) superparamagnetic iron oxide nanoparticles (SPION) for targeted destruction of cancer cells, and ii) poly(N-isopropylacrylamide) (pNIPAM) coated magnetic particles (MNP) for multistage cell separation.
SPION are generally considered as drug delivery vehicles for the enhanced permeability and retention (EPR) effect. SPION possess the intrinsic peroxidase-like activity as Horseradish peroxidase (HRP), which can generate reactive oxygen species (ROS) from H2O2 via Fenton’s reaction. ROS regulate cell signaling, but a significant ROS stress can disrupt the redox homeostasis of cancer cells leading to selective tumor cell toxicity and destruction. Hereby, we developed ROS-induced targeted cell destruction with SPION-GOx bioconjugates platform. GOx catalyzes glucose oxidation in cancer cells to produce H2O2. 24 h incubation with 10 μg/mL SPION-GOx on 4T1 cells resulted in almost zero cell viability. In vivo evaluation showed SPION-GOx led to a much slower tumor growth compared to control groups.
Additionally, magnetic activated cell sorting (MACS) has become a common technique for the separation of target cell populations from biological suspensions. A major obstacle preventing current single stage MACS from achieving satisfying separation efficiency is the non-specific interactions between the cells and MNP. Thus, we designed a multistage separation platform similar to distillation concept in chemical engineering. The repeated capture-and-release separation process is enabled by attaching the temperature responsive polymer- pNIPAM to both MNP and target cells. We manipulate the reversible hydrophobic-hydrophilic interactions between such functionalized MNP and target cells through temperature cycling to capture and release target cells at a higher efficiency than non-target. After several temperature cycles, target cells are enriched in the product. Flow cytometry results suggest that A431 cells (target) could be effectively separated from HeLa cells (non-target) after three separation stages resulting in an enrichment factor of 3.69 when the starting ratio of target to non-target is 1:2.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Zhao, Jiaqijiz105@pitt.edujiz105
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLi, Leilel55@pitt.edulel55
Committee MemberEnick, Robertrme@pitt.edurme
Committee MemberFullerton, Susanfullerton@pitt.edufullerton
Committee MemberZeng, Dexingzengd@ohsu.eduzengd
Date: 24 June 2019
Date Type: Publication
Defense Date: 16 November 2017
Approval Date: 24 June 2019
Submission Date: 5 April 2018
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 127
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Chemical Engineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Fe3O4 nanoparticles, SPION, ROS, cancer therapy, cell separation, pNIPAM, MACS, cell destruction, GOx, multistage separation
Date Deposited: 24 Jun 2019 18:44
Last Modified: 24 Jun 2020 05:15


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