Description

• Title:
  Properties and application of tyrosine-modified and unmodified polyethyleneimine polymers as siRNA carriers
• Creator:
  Kubczak, Małgorzata
• Contributor:
  Uniwersytet Łódzki, Wydział Biologii i Ochrony Środowiska, Katedra Biofizyki Ogólnej
• Description:
  RNA interference (RNAi)-based therapy is a promising treatment option for many diseases, including cancer, neurodegenerative disorders and auto-immune diseases. RNAi may target a selected gene, allowing to avoid adverse effects related to standard treatment options. Due to its specificity, RNAi technology may be useful for the treatment of so-called ‘undruggable’ genes. Strategies based on RNAi have been broadly explored. Currently, increasing numbers of studies focus on the improvement of nanomedicines. Among many available nanocarriers for siRNA, cationic polymers gain special attention, due to efficient and non-toxic delivery mechanisms. As positively charged particles, they show improved interaction with negatively charged cell membranes and enhanced cellular uptake. The aim of the current work was to describe the properties of polyethyleneimines (PEIs) and their tyrosine modified counterparts. The first step focused on the evaluation of the biophysical properties of PEIs, their toxicity and ability to form complexes with siRNA. Linear and branched, tyrosine modified polymers complexed siRNA at favorable mass ratios which allowed significant gene expression knockdown with a limited cytotoxicity. Tyrosine modified PEIs were investigated in the further steps. The second task included a better understanding of complex formation, toxicity mechanisms and gene knockdown efficacy. The third task aimed to describe biophysical properties of tyrosine modified polymer: human serum albumin interactions. Summarizing, tyrosine modification significantly affected the properties of polyethyleneimines, changing their toxicity profile, siRNA binding capacity and interaction with human serum albumin. Tyrosine modified polymers performed better as siRNA carriers, exhibiting acceptable toxic effects and a very promising knockdown efficiency.
• Object availability:
  free access
• Rights: http://creativecommons.org/licenses/by-nc-nd/4.0 ;
  Attribution-NonCommercial-NoDerivatives 4.0 Międzynarodowe
• Date:
  2023.10.17;
  2023;
  2023.12.04
• Type:
  PhD/Doctoral Dissertation
• Language:
  English
• Format:
  application/pdf
• Subject:
  polyethylenimines;
  tyrosine modification;
  gene therapy;
  siRNA delivery
• Identifier: http://hdl.handle.net/11089/48094
• Data provider:
  Repozytorium Uniwersytetu Łódzkiego
• Can I use it?:
  seek permission
• Type:
  text