Advanced

REGULATED UPTAKE OF BIOPOLYMERS Role of cell surface proteoglycans Implications for drug and gene delivery

Sandgren, Staffan LU (2005)
Abstract
Cells continuously export, import, and recycle molecules over the plasma membrane. Internalization, i.e. cellular import of extracellular material, is a fundamental process, which provides cells with nutrients and enables the immune cells of higher organisms to remove debris, sample their surroundings for antigens and to fight microbes. Moreover, internalization regulates complex cellular signalling events involved in cellular division, motion, and communication with the surrounding extracellular matrix. However, the preserved routes of internalization are exploited by a large number of microbes and pathological factors such as bacterial toxins and viral proteins. The HIV-1 TAT protein was shown to enter cells and to target their nuclei,... (More)
Cells continuously export, import, and recycle molecules over the plasma membrane. Internalization, i.e. cellular import of extracellular material, is a fundamental process, which provides cells with nutrients and enables the immune cells of higher organisms to remove debris, sample their surroundings for antigens and to fight microbes. Moreover, internalization regulates complex cellular signalling events involved in cellular division, motion, and communication with the surrounding extracellular matrix. However, the preserved routes of internalization are exploited by a large number of microbes and pathological factors such as bacterial toxins and viral proteins. The HIV-1 TAT protein was shown to enter cells and to target their nuclei, thus acting as a paracrine transcription factor, a finding that initiated the field of so called cell penetrating peptides (CPPs). Due to their ability to efficiently deliver macromolecular cargo over the plasma membrane, CPPs have proven to be useful tools in basic research. More importantly, the technology has been shown to enhance delivery of a number of macromolecular compounds in vivo, including anticancer drugs.



The proteoglycan family of molecules has previously been shown to participate in the interaction with and internalization of a number of ligands, including polyamines, growth factors, morphogens, and microbes. This thesis deals with the role of proteoglycans in cellular internalization of charged biopolymers, i.e. the polyamine family of growth factors, HIV-Tat peptide, antimicrobial peptides, and nucleic acids. The presented findings bring proteoglycans into focus as a general internalization pathway for charged macromolecules, with implications for drug and gene delivery. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor Lebleu, Bernard, Laboratoire des Défenses Antivirales et Antitumorales, Université Montpellier II, Montpellier, Franc
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Medicin (människa och djur), Cytology, oncology, proliferation, differentiation, Medicine (human and vertebrates), growth factor, cancer, drug delivery, gene therapy, LL-37, HIV-Tat, cell penetrating peptides, polyamines, heparan sulfate, onkologi, Cytologi, cancerology, internalization, proteoglycans
pages
143 pages
publisher
Staffan Sandgren Department of Experimental Medical Science Medical Faculty Lund University
defense location
GK-salen BMC Sölvegatan 19 Lund
defense date
2005-10-14 09:00
ISSN
1652-8220
ISBN
91-85439-77-0
language
English
LU publication?
yes
id
9f24a326-81b1-4c5a-acbc-ee8080a39c1c (old id 545423)
date added to LUP
2007-09-25 10:10:48
date last changed
2016-09-19 08:44:56
@phdthesis{9f24a326-81b1-4c5a-acbc-ee8080a39c1c,
  abstract     = {Cells continuously export, import, and recycle molecules over the plasma membrane. Internalization, i.e. cellular import of extracellular material, is a fundamental process, which provides cells with nutrients and enables the immune cells of higher organisms to remove debris, sample their surroundings for antigens and to fight microbes. Moreover, internalization regulates complex cellular signalling events involved in cellular division, motion, and communication with the surrounding extracellular matrix. However, the preserved routes of internalization are exploited by a large number of microbes and pathological factors such as bacterial toxins and viral proteins. The HIV-1 TAT protein was shown to enter cells and to target their nuclei, thus acting as a paracrine transcription factor, a finding that initiated the field of so called cell penetrating peptides (CPPs). Due to their ability to efficiently deliver macromolecular cargo over the plasma membrane, CPPs have proven to be useful tools in basic research. More importantly, the technology has been shown to enhance delivery of a number of macromolecular compounds in vivo, including anticancer drugs.<br/><br>
<br/><br>
The proteoglycan family of molecules has previously been shown to participate in the interaction with and internalization of a number of ligands, including polyamines, growth factors, morphogens, and microbes. This thesis deals with the role of proteoglycans in cellular internalization of charged biopolymers, i.e. the polyamine family of growth factors, HIV-Tat peptide, antimicrobial peptides, and nucleic acids. The presented findings bring proteoglycans into focus as a general internalization pathway for charged macromolecules, with implications for drug and gene delivery.},
  author       = {Sandgren, Staffan},
  isbn         = {91-85439-77-0},
  issn         = {1652-8220},
  keyword      = {Medicin (människa och djur),Cytology,oncology,proliferation,differentiation,Medicine (human and vertebrates),growth factor,cancer,drug delivery,gene therapy,LL-37,HIV-Tat,cell penetrating peptides,polyamines,heparan sulfate,onkologi,Cytologi,cancerology,internalization,proteoglycans},
  language     = {eng},
  pages        = {143},
  publisher    = {Staffan Sandgren Department of Experimental Medical Science Medical Faculty Lund University},
  school       = {Lund University},
  title        = {REGULATED UPTAKE OF BIOPOLYMERS Role of cell surface proteoglycans Implications for drug and gene delivery},
  year         = {2005},
}