Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment

High-Z nanoparticles have been studied over the years as a potential radio-theranostic agent due to their high X-ray absorption and good pharmacokinetic properties. However, only a few platinum-based agents have been reported in the literature, despite its wide usage in chemotherapy (i.e., cisplatin...

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Main Author:	Anuar, Muhammad Afiq Khairil
Format:	Thesis
Language:	English
Published:	2021
Subjects:	R Medicine
Online Access:	http://eprints.usm.my/52045/1/MUHAMMAD%20AFIQ%20BIN%20KHAIRIL%20ANUAR-FINAL%20THESIS%20P-SKD000216%28R%29%20PWD_-24%20pages.pdf
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spelling	my-usm-ep.520452022-03-27T04:00:06Z Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment 2021-10 Anuar, Muhammad Afiq Khairil R Medicine High-Z nanoparticles have been studied over the years as a potential radio-theranostic agent due to their high X-ray absorption and good pharmacokinetic properties. However, only a few platinum-based agents have been reported in the literature, despite its wide usage in chemotherapy (i.e., cisplatin). Thus, this work aims to study platinum nanoparticles, Platinum Nanodendrites (PtND), as a novel theranostic agent. The PtNDs fabricated in this work possessed a dendritic shape with a negatively charged surface. Four PtND sizes were prepared for theranostic evaluations (29 nm, 36 nm, 42 nm, and 52 nm). In-vitro biocompatibility assessment revealed that the PtNDs of all sizes were non-cytotoxic for the particle concentration of up to 0.1 mM. Furthermore, the PtNDs’ toxicity also depended on PtNDs’ size, cell type, and incubation period. The theranostic evaluation of PtNDs was separated into diagnostic and radiotherapy sections. The diagnostic evaluation was performed with the maximum available PtND concentration, 1.0 mM, to maximize their image contrast in X-ray images. The PtNDs of different sizes were compared with the commercial iodinated contrast agent in three X-ray modalities (CT, fluoroscopy, and planar X-ray). The result in all imaging systems evidenced better attenuation of PtNDs over iodinated contrast agent at equivalent concentration. The contrast enhancement is also size-dependent, where larger PtNDs exhibited higher X-ray attenuation than the smaller ones. The radiotherapy evaluation involved a study on the radiosensitization effects of PtNDs in three different types of radiotherapy: 6 MV photon radiotherapy, 6 MeV electron beam therapy, and 150 MeV proton beam therapy. HeLa cells were treated with 0.1 mM of PtNDs of different sizes and subjected to increasing radiation doses. The clonogenic assay evaluations revealed that the PtNDs successfully enhanced the radiosensitivity of HeLa cells, depending on the particle size and types of radiotherapy. The maximum radiosensitization effect was observed in the combination of 29 nm PtNDs with PhT (SER=2.54). 36 nm and 42 nm PtNDs produced the highest radiosensitization in PrT (SER=1.38) and EBT (SER=1.83), respectively. DCF assay assessment shows that the ROS induced by the PtND-radiation combinations may not be the major determining factors that catalyse the PtNDs’ radiosensitization effect. In conclusion, this work has successfully developed and characterized the theranostic potential of PtNDs. This study provides a platform for theranostic multimodal approaches in diagnostic imaging and radiotherapy to improve cancer treatment efficacy and outcomes. 2021-10 Thesis http://eprints.usm.my/52045/ http://eprints.usm.my/52045/1/MUHAMMAD%20AFIQ%20BIN%20KHAIRIL%20ANUAR-FINAL%20THESIS%20P-SKD000216%28R%29%20PWD_-24%20pages.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R Medicine
spellingShingle	R Medicine Anuar, Muhammad Afiq Khairil Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment
description	High-Z nanoparticles have been studied over the years as a potential radio-theranostic agent due to their high X-ray absorption and good pharmacokinetic properties. However, only a few platinum-based agents have been reported in the literature, despite its wide usage in chemotherapy (i.e., cisplatin). Thus, this work aims to study platinum nanoparticles, Platinum Nanodendrites (PtND), as a novel theranostic agent. The PtNDs fabricated in this work possessed a dendritic shape with a negatively charged surface. Four PtND sizes were prepared for theranostic evaluations (29 nm, 36 nm, 42 nm, and 52 nm). In-vitro biocompatibility assessment revealed that the PtNDs of all sizes were non-cytotoxic for the particle concentration of up to 0.1 mM. Furthermore, the PtNDs’ toxicity also depended on PtNDs’ size, cell type, and incubation period. The theranostic evaluation of PtNDs was separated into diagnostic and radiotherapy sections. The diagnostic evaluation was performed with the maximum available PtND concentration, 1.0 mM, to maximize their image contrast in X-ray images. The PtNDs of different sizes were compared with the commercial iodinated contrast agent in three X-ray modalities (CT, fluoroscopy, and planar X-ray). The result in all imaging systems evidenced better attenuation of PtNDs over iodinated contrast agent at equivalent concentration. The contrast enhancement is also size-dependent, where larger PtNDs exhibited higher X-ray attenuation than the smaller ones. The radiotherapy evaluation involved a study on the radiosensitization effects of PtNDs in three different types of radiotherapy: 6 MV photon radiotherapy, 6 MeV electron beam therapy, and 150 MeV proton beam therapy. HeLa cells were treated with 0.1 mM of PtNDs of different sizes and subjected to increasing radiation doses. The clonogenic assay evaluations revealed that the PtNDs successfully enhanced the radiosensitivity of HeLa cells, depending on the particle size and types of radiotherapy. The maximum radiosensitization effect was observed in the combination of 29 nm PtNDs with PhT (SER=2.54). 36 nm and 42 nm PtNDs produced the highest radiosensitization in PrT (SER=1.38) and EBT (SER=1.83), respectively. DCF assay assessment shows that the ROS induced by the PtND-radiation combinations may not be the major determining factors that catalyse the PtNDs’ radiosensitization effect. In conclusion, this work has successfully developed and characterized the theranostic potential of PtNDs. This study provides a platform for theranostic multimodal approaches in diagnostic imaging and radiotherapy to improve cancer treatment efficacy and outcomes.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Anuar, Muhammad Afiq Khairil
author_facet	Anuar, Muhammad Afiq Khairil
author_sort	Anuar, Muhammad Afiq Khairil
title	Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment
title_short	Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment
title_full	Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment
title_fullStr	Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment
title_full_unstemmed	Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment
title_sort	novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Perubatan
publishDate	2021
url	http://eprints.usm.my/52045/1/MUHAMMAD%20AFIQ%20BIN%20KHAIRIL%20ANUAR-FINAL%20THESIS%20P-SKD000216%28R%29%20PWD_-24%20pages.pdf
_version_	1747822128804134912

Novel multifunctional platinum nanodendrites as theranostic agents in cancer imaging and radiotherapy treatment

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