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Abstract
The objective of this thesis is to synthesize nanoparticles based on the technique of albumin-polymer conjugation which will subsequently be used to fabricate the controlled drug carriers for cancer therapeutics. Albumin-polymer conjugates exhibit desirable properties tailored by polymerizing different monomers according to the requirement to delivery of different drugs.
When bovine serum albumin (BSA) as a model albumin was conjugated with hydrophobic polymers (e.g. poly (methyl methacrylate) (PMMA) and polycaprolactone (PCL)), giant amphiphilic architectures could be developed, leading to the formation of new type of micelles or other aggregates, which stems from their self-assembly in aqueous media. In the meantime, some hydrophobic anticancer drugs could be encapsulated into the polymeric core, such as curcumin and albendazole. The obtained nanoparticles demonstrated a well-defined spherical structure with a diameter of 100-150 nm. Especially, the BSA-PCL nanoparticles are biocompatible and biodegradable with high drug loading efficiency and storage stability. Our results showed that albumin introduces an element of selectivity towards cancer cell lines and the healthy cells are less affected while the polymeric nanoparticles based on polymers lead to even higher toxicity to healthy cells compared to cancerous cells.
We extended the application of albumin-polymer nanoparticles for the transfection of oligonucleotides. The hydrophilic cationic polymer was used to replace the hydrophobic polymer to condense with the anionic oligonucleotide and the design of the carriers still remained the selectivity towards cancerous cells. Novel biocompatible polyion complex nanoparticles, containing BSA, cationic polymer and oligonucleotide, were synthesized as a generation of vectors for the oligonucleotide transfection.
In addition, the negative charged albumin can also be used to condense and delivery positive charged protein drug. PEGylation can improve the pharmaceutical properties of the albumin polyplex.
As a conclusion, the applications of albumin-polymer conjugates as a delivery system will be a significant addition to the new generation of cancer treatment and even imaging. This fusion of biological and chemical properties establishes a critical role of albumin-polymer conjugates in the intersection of chemistry, biotechnology, nanotechnology, and medicine.