Synthesis Of Supramolecular Self-assembly With Biological Testing Or Drug Release Function

To prepare small molecules or polymer biomaterials, self-assembly was considered as an importantfactor in the design of its nanostructure for achievingmultiple functionalities. Among the many motifs for building-up novel biofunctional materials, amino acids and peptides have attracted intensive research attention in recent years due to its biocompatibility, biodegradability, easy functionalization and diversity.In this thesis, we expected to evaluate the self-assembly properties of amino acids and peptides based biomaterials, as well as its efficacy in enzyme detectionorcontrolled drug release.In the first part of this study, we simply combinedtetraphenylethylene with tyrosine-phosphate to generate a new amphiphile,which not only underwent enzymatic dephosphorylation to generate a relative hydrophobic residuefor alkaline phosphatase(ALP) detection with significant enhancement of the fluorescence signals,but also self-assembled in water to result in a novel supramolecular hydrogel with gelationenhancedfluorescence emission features upon the changes of pH. In addition, the highly orderedmicelle nanostructures self-assembled from this amphiphile exhibited the ability to serve as efficienttemplates to promote the nucleation and growth of calcium phosphate.In the second part of this study, we reported the generation of a novel self-assembled platinum(Pt)prodrug froma short peptide derivative, which acted as a substrate forthe phosphatase-catalyzed dephosphorylation reaction, and a Pt(IV)complex, which could undergo supramolecular self-assembly in thepresence of alkaline phosphatase, andperform controlled release ofthe Pt(II) drug under the reductive conditions of tumor cells.In vivo biodistribution, tumor inhibition examination andhematoxylin and eosin(H&E) staining demonstrated thatself-assembled anticancer prodrug exhibitedsignificant antitumor growth effects, but muchlower toxicity towards the kidney, liver, spleen and other major organsthan the free cisplatin drug in mice. Such improved antitumor efficacycould be ascribed to the localized and sustained release of the Pt(II)anticancer drug from the supramolecular self-assembly of the Pt(IV)prodrug, which was triggered by phosphatases in tumor sites.