Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli

This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluo...

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Main Author:	Musalli, Abdul Hadi
Format:	Thesis
Language:	English
Published:	2020
Subjects:	Clinical pathology Laboratory technique
Online Access:	https://ir.uitm.edu.my/id/eprint/59684/1/59684.pdf
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spelling	my-uitm-ir.596842022-05-17T03:01:45Z Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli 2020-10 Musalli, Abdul Hadi Clinical pathology. Laboratory technique This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluorouracil were synthesized by carbodiimide chemistry and prepared by nanospray drying technique respectively. The cellular internalization profiles of oligochitosan-folate nanoparticles against the human malignant melanoma cell line (SKMEL-28) were evaluated using confocal scanning electron microscopy technique through fluorescence labelling and endocytic inhibition, as a function of nanoparticulate folate content, size, polydispersity index, zeta potential, shape, surface roughness and folate population density. The cytotoxicity and cell cycle arrest characteristics of oligochitosan-folate-carboxymethyl-5-fluorouracil nanoparticles, prepared with an optimal folate content that promoted cellular internalization, were evaluated against the oligochitosan-folate and oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles. The oligochitosan-folate conjugate nanoparticles were endocytosed by melanoma cells via caveolae- and lipid raft-mediated endocytic pathways following them binding to the cell surface folate receptor. Nanoparticles that were larger and with higher folic acid contents and zeta potentials exhibited a higher degree of cellular internalization. Excessive conjugation of nanoparticles with folate resulted in a high nanoparticulate density of folate which hindered nanoparticles-cell interaction via folate receptor binding and reduced cellular internalization of nanoparticles. Conjugating oligochitosan with 20 %w/w folate was favorable for cellular uptake as supported by in silico models. Conjugating of oligochitosan nanoparticles with carboxymethyl-5-fluorouracil and 20 %w/w of folate promoted nanoparticles-folate receptor binding, cellular internalization and cancer cell death via cell cycle arrest at S phase at a lower drug dose than oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles and neat carboxymethyl-5-fluorouracil. 2020-10 Thesis https://ir.uitm.edu.my/id/eprint/59684/ https://ir.uitm.edu.my/id/eprint/59684/1/59684.pdf text en public masters Universiti Teknologi MARA Faculty of Pharmacy Wong, Tin Wui (Prof. Dr.)
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Wong, Tin Wui (Prof. Dr.)
topic	Clinical pathology Laboratory technique
spellingShingle	Clinical pathology Laboratory technique Musalli, Abdul Hadi Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli
description	This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluorouracil were synthesized by carbodiimide chemistry and prepared by nanospray drying technique respectively. The cellular internalization profiles of oligochitosan-folate nanoparticles against the human malignant melanoma cell line (SKMEL-28) were evaluated using confocal scanning electron microscopy technique through fluorescence labelling and endocytic inhibition, as a function of nanoparticulate folate content, size, polydispersity index, zeta potential, shape, surface roughness and folate population density. The cytotoxicity and cell cycle arrest characteristics of oligochitosan-folate-carboxymethyl-5-fluorouracil nanoparticles, prepared with an optimal folate content that promoted cellular internalization, were evaluated against the oligochitosan-folate and oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles. The oligochitosan-folate conjugate nanoparticles were endocytosed by melanoma cells via caveolae- and lipid raft-mediated endocytic pathways following them binding to the cell surface folate receptor. Nanoparticles that were larger and with higher folic acid contents and zeta potentials exhibited a higher degree of cellular internalization. Excessive conjugation of nanoparticles with folate resulted in a high nanoparticulate density of folate which hindered nanoparticles-cell interaction via folate receptor binding and reduced cellular internalization of nanoparticles. Conjugating oligochitosan with 20 %w/w folate was favorable for cellular uptake as supported by in silico models. Conjugating of oligochitosan nanoparticles with carboxymethyl-5-fluorouracil and 20 %w/w of folate promoted nanoparticles-folate receptor binding, cellular internalization and cancer cell death via cell cycle arrest at S phase at a lower drug dose than oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles and neat carboxymethyl-5-fluorouracil.
format	Thesis
qualification_level	Master's degree
author	Musalli, Abdul Hadi
author_facet	Musalli, Abdul Hadi
author_sort	Musalli, Abdul Hadi
title	Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli
title_short	Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli
title_full	Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli
title_fullStr	Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli
title_full_unstemmed	Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli
title_sort	cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / abdul hadi musalli
granting_institution	Universiti Teknologi MARA
granting_department	Faculty of Pharmacy
publishDate	2020
url	https://ir.uitm.edu.my/id/eprint/59684/1/59684.pdf
_version_	1783735046231818240

Cellular uptake of chitosan-folate-carboxymethyl 5-fluorouracil conjugate nanoparticles by malignant melanoma cells / Abdul Hadi Musalli

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