Polymer-Coated Nanodiamonds for Drug Delivery

Abstract

Nanodiamonds (NDs) are promising candidates for drug delivery due to their small size, biocompatibility and stable fluorescence. Their large surface area and ease of functionalization allow the surface to be functionalized with various bioactive compounds. However, the strong tendency to form aggregates in aqueous environment limits their bio-applications. In this Thesis, NDs were coated with synthetic hydrophilic polymers to improve both colloidal stability and to create sites accommodating for anticancer drugs. Several issues exist with the direct administration of anticancer drugs, amongst these are the severe systemic side effects and metabolization before reaching the diseased sites. Incorporating the drugs into nanoparticles presents an elegant method to protect drugs from metabolism and minimize side effects. A gemcitabine prodrug monomer with a pH or glutathione (GSH) responsive linkage was incorporated into a polymer by RAFT polymerization. The polymer was then grafted onto the surface of NDs by copper free click chemistry or supramolecular chemistry. Melittin was encapsulated onto the surface functionalized with polymer containing carboxylic acids via electrostatic interactions. When the surface of NDs was functionalized with ?-cyclodextrin conjugated polyacrylic acid, the positively charged doxorubicin and paclitaxel-loaded polymer with adamantane end group were loaded onto the surface simultaneously. After internalization into cancer cells, the nanoparticles loaded with drugs can release their payloads responsive to the intracellular microenvironment, such as a decrease in pH or an increase in GSH concentration. Additionally, these drugs are mostly retained in the nanoparticles before uptaken by cells, allowing for the on-demand delivery of the encapsulated drugs. Cleavable linkages were employed for gemcitabine and paclitaxel whilst melittin and doxorubicin were loaded electrostatically. Both these methods released the respective drugs in their original form, hence preserving the therapeutic efficacy of these drugs.