Biodegradable Nanoparticles Based on Aliphatic Polyesters; Towards Targeted Intracellular Delivery of Protein Therapeutics

N. Samadi

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

Abstract

Many proteins and peptides possess specific biological activity that makes them potentially suitable as therapeutic agent for the treatment of various severe chronic and life-threatening diseases such as cancer. However, some pharmaceutical proteins have their target intracellularly. For the intracellular delivery of proteins/peptides, particularly for the ones that do not passively pass cellular membranes, suitable carrier systems such as polymeric nanoparticles (NPs) are required. In our study, the suitability of NPs based on a new type of polyester polymer for the controlled release and targeted intracellular delivery of (therapeutic) proteins was explored. Our results demonstrated that the release pattern of the embedded protein can be effectively modulated by changing polymer properties. Ribonucleases are small (10–28 kDa) basic proteins which are able to catalyze the degradation of cytosolic RNAs. Therefore these proteins have raised attention in the biopharmaceutical and medical field for use as novel anti-cancer therapeutics. The Her2 (or EGFR2; human epidermal growth factor receptor 2) receptor is overexpressed in aggressive types of breast cancer cells and has become in recent years an important target for therapy. RNase-loaded and nanobody conjugated NPs showed higher cellular binding and cytotoxicity as compared to non-conjugated NPs. These results demonstrate that ribonuclease was released intracellularly where it could catalyze the degradation of cytosolic RNAs resulting in cell killing. These findings are promising for effective delivery of anti-cancer agents.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Utrecht University
Supervisors/Advisors
  • Hennink, Wim, Primary supervisor
  • van Nostrum, Rene, Co-supervisor
  • Amidi, M., Co-supervisor
Award date14 Apr 2014
Publisher
Print ISBNs978-90-393-6134-4
Publication statusPublished - 14 Apr 2014

Fingerprint

Dive into the research topics of 'Biodegradable Nanoparticles Based on Aliphatic Polyesters; Towards Targeted Intracellular Delivery of Protein Therapeutics'. Together they form a unique fingerprint.

Cite this