Molecularly Targeted Photothermal Ablation of Epidermal Growth Factor Receptor-Expressing Cancer Cells with a Polypyrrole-Iron Oxide-Afatinib Nanocomposite

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TMUIR > College of Biomedical Engineering > International Ph.D. Program in Biomedical Engineering > Thesis > Item 987654321/63186

Please use this identifier to cite or link to this item: http://libir.tmu.edu.tw/handle/987654321/63186

Title:	Molecularly Targeted Photothermal Ablation of Epidermal Growth Factor Receptor-Expressing Cancer Cells with a Polypyrrole-Iron Oxide-Afatinib Nanocomposite
Authors:	LEKSHMI, R
Contributors:	��ڥ��u�{�դh�Ǧ�ǵ{ Lu, Long�VSheng Chuang, Er-Yuan
Keywords:	Polypyrrole;Iron oxide;Afatinib;EGFR;Photothermal therapy
Date:	2022-12-22
Issue Date:	2023-12-07 09:54:04 (UTC+8)
Abstract:	The cancer treatment method NIR-PTT, or near infrared-photothermal therapy, shows promise. The therapeutic index might be improved by guiding the thermal effect of NIR solely to cancer cells for the best possible treatment outcome. It is yet unknown if EGFR is being targeted by nanoparticles tethered to tyrosine kinase inhibitors (TKI) may drive NIR-PTT to malignancies with cellular accuracy, even though EGFR is typically overexpressed or genetically altered in human malignancy. The polypyrrole-iron oxide-afatinib nanocomposite (PIA-NC) was created to test this hypothesis. In the PIA-NC, a TKI (afatinib) that binds to overexpressed wild-type EGFR without obviously causing harm was combined with a biocompatible and photothermal conductive polymer (polypyrrole). A variety of physical and chemical characterizations were carried out through experiments. Particle internalization, cytotoxicity, ROS production, and apoptosis in EGFR-positive and EGFR-negative cell lines were investigated in both the presence and absence of NIR. We found that the PIA-NCs were stable at +35 mV zeta potential and 243 nm size. These PIA-NCs were swiftly absorbed near the cell membrane by all the cell types examined in the study. The Fourier transform infrared spectra and electron dispersion spectrum revealed that afatinib is chemically conjugated to the NC but not iron oxide. At a low NIR-PTT energy level, PIA-NC significantly increases the sensitivity of EGFR overexpressed A549 lung cancer cells to NIR-PTT-induced cytotoxicity but not in EGFR-negative 3T3 fibroblasts. Intracellular ROS increased one minute after the NIR-PTT, followed by the induction of early cellular apoptosis. Our findings confirmed that a molecularly targeted NC provides a deliberate platform for the targeted administration of NIR-PTT to cancer cells. The geometric proximity design suggests an innovative method to lessen the physiological effects of NIR-off-target PTT. It is crucial to look into how PIA-NC may be improved for real-life application.
Description:	�դh ��ɱб�:Lu, Long�VSheng �@�P��ɱб�:Chuang, Er-Yuan �e��:Sun,Chia Wei �e��:Chiang,Wei Hung �e��:Pan ,Wen Yu �e��:Lu, Long�VSheng �e��:Chuang, Er-Yuan
Data Type:	thesis
Appears in Collections:	[International Ph.D. Program in Biomedical Engineering] Thesis

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