| Summary: | 博士 === 高雄醫學大學 === 醫藥暨應用化學系博士班 === 105 === Dendrimers hold great promise for a wide range of applications thanks to their unique structural architecture and multivalent cooperativity. Unfortunately, dendrimer synthesis often suffers from inherent problems of structural defects caused by incomplete reactions and difficulties associated with dendrimer purification because of the presence of highly similar side-products. For these reasons, alternative synthetic approaches to overcome the limitations of current dendrimer synthesis are in high demand. The objective of my PhD thesis is to contribute to advances in dendrimer synthesis by exploring solid-phase method and self-assembly approaches to enable the creation of structurally diverse dendrimers as new molecular paradigms and functional materials for future applications, in particular in the biomedical field.
The first part of my PhD project mainly focuses on establishing novel strategies and methodologies for solid-phase dendrimer synthesis (SPDS) because SPDS has advantages of convenient synthesis and easy purification procedures. We first developed a new and concise solid-phase synthesis of PAMAM dendrimers based on the adoption of peptide synthesis chemistry. High-generation dendrimers were successfully achieved using solid supports with a reduced loading ratio. We then constructed a small library of triazine dendrimers varying in generations and surface groups with a view to rapidly synthesizing dendrimers with structural diversity. We also strived to synthesize poly(aminoester) dendrimers using the solid-phase method. However, due to the labile nature of poly(aminoester) dendrimers, we were not able to obtain the desired dendrimers. We are still pursuing our efforts in this direction.
The second part of my PhD program aims to apply the self-assembly approach for constructing supramolecular dendrimers, because self-assembly is a powerful yet convenient strategy to create supramolecular nanoassemblies. In particular, we would like to build a supramolecular dendrimer nanosystem as a nanotheranostic for simultaneous molecular imaging and drug delivery. For this purpose, a small DOTA-conjugated amphiphilic dendrimer with Gd(III)-chelation has been established. This dendrimer was able to self-assemble into supramolecular dendrimer nanomicelles to encapsulate the anticancer drug doxorubicin in the interior, while at the same time bearing Gd/DOTA-entities on the dendrimer surface. It constitutes a novel multivalent nanotheranostic to improve imaging sensitivity and resolution as well as therapeutic efficacy.
In summary, my PhD program mainly contributes to elaborating strategies for dendrimer synthesis using both solid-phase method and self-assembly approach. Results from these studies have allowed us to advance dendrimer synthesis and will further help us to improve our knowledge with a view to constructing versatile dendritic molecules and broaden their applications in the arenas of biomedical and material sciences.
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