With the remarkable advancement in the nanoparticles (NPs)-based drug
delivery systems (DDS) over the past several decades, the pharmacological properties
associated with conventional free drugs delivery are improved. In this thesis, we report
potential candidates for the next-generation NP-based DDS.
While natural DDS are promising as they possess exceptional delivery
mechanisms and selective targeting, synthetic DDS are more favorable for their low
immunogenicity. Our developed natural DDS called magnetotactic bacterial cages
(MBC), which is based on magnetotactic bacteria (MTB) as a guidable delivery vehicle for
DNA functionalized gold nanoparticles (AuNPs). Loading DNA functionalized AuNPs in
MTB aided in increasing the maximum-tolerated dose of DNA functionalized AuNPs and
tackled issues related to DNA functionalized AuNPs stability and systemic delivery.
Natural DDS hold great advantages; however, it is difficult to make complete prediction
about their immunogenicity and toxicity on the basis of preclinical trials. Thus, we
assessed the efficacy of synthetic NP-based DDS.
Using inorganic platforms, we were able to develop the first visual monitoring
system of bacteria-NPs interaction. The system offers simultaneous sensing and
inhibition of bacteria in infected cells. The system is comprised of Au nanoclusters
@lysozyme (AuNC@lys) colloids MSN loaded with antibacterial agents. The applicability
of the inorganic DDS in the biomedical field has been limited by the high
Hybrid materials combine the advantages of organic, inorganic and natural
carriers, offering opportunities for enhanced stability, manipulating release behavior
and combine two or more functions in a single platform. To further enhance the
properties our inorganic DDS, we incorporated light-responsive organic ligands to silicabased
NPs. Plasmid DNA was loaded on the light-responsive bridged silsesquioxane
nanocomposites (BS NPs). Light irradiation was performed to reverse the surface charge
of NPs via a photoreaction of the organic fragments (silsesquioxane) within the NPs, that
resulted in the release of plasmid DNA in HeLa cancer cells. Finally, we assessed a new
class of organic-inorganic DDS composed of inorganic metal ions and organic linkers,
zeolite imidazolate frameworks-8 (ZIF-8). These NPs showed exceptional ability to
entrap large cargo due to their tunable porosity and structural flexibility.
|Date of Award||Oct 2018|
- Biological, Environmental Science and Engineering
|Supervisor||Niveen Khashab (Supervisor)|