Polymeric nanoparticles for intracellular drug delivery

Abstract

Polymeric nanoparticle is a competitive candidate in intracellular drug delivery. However, limited understanding of the effects of physicochemical parameters on particle-cell interaction and intracellular trafficking hampers its further improvements. In this thesis, I mainly focus on: 1) Providing concise methods in controlling size, morphology and surface modification of polymeric nanoparticles; 2) Investigating the intracellular trafficking of polymeric nanoparticles with different surface modifications; 3) Designing oligoarginine-modified nanoparticles for intracellular drug delivery applications. I firstly demonstrated the conditions to produce uniformed submicron polymeric particles, and introduced a robust and efficient method for submicron polymeric vesicle formation, named as temperature-assisted nanoprecipitation (TAN). Furthermore, I designed and synthesized different oligoarginine-modified poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) polymeric nanoparticles through click chemistry, and investigated how the length and density of oligoarginine influences the cellular uptake and intracellular trafficking. Changing the length of oligoarginine not only affects the cellular uptake capacity of polymeric nanoparticles, but also determines the endocytic pathways, the endosomal escape capacity and subcellular trafficking. On the other hand, decreasing the oligoarginine density on particle surface only lowers the amount of uptake and endosomal escape, but does not alter the endocytic pathways and subcellular trafficking of the particles. Finally, oligoarginine-modified nanoparticle system was further modified for different applications, including mitochondria-targeting delivery of doxorubicin and the encapsulation of DB213.

Date of Award	2015
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology