Self-assembly is an effective approach for nanoparticle fabrication. An easy, robust and versatile approach is highly sought after for constructing drug nanocarriers with desired biophysicochemical properties. In this thesis work, we present two self-assembling strategies to construct nanoparticles from small aromatic molecules and evaluate them as drug carriers. The 9-fluorenylmethoxycarbonyl (Fmoc) group is employed and their aromatic interactions enable a rapid and efficient self-assembly....[ Read more ]

Self-assembly is an effective approach for nanoparticle fabrication. An easy, robust and versatile approach is highly sought after for constructing drug nanocarriers with desired biophysicochemical properties. In this thesis work, we present two self-assembling strategies to construct nanoparticles from small aromatic molecules and evaluate them as drug carriers. The 9-fluorenylmethoxycarbonyl (Fmoc) group is employed and their aromatic interactions enable a rapid and efficient self-assembly.

Firstly, microemulsion techniques were utilized to control self-assembly of Fmoc-dipeptides, and nanoparticles of around 6 nm were fabricated. This small size is favorable for carriers to pass through tight junction barriers, but unfavorable for systemic cancer therapy (optimal size between 10 and 200 nm). In the second strategy, a simple trigonal Fmoc-conjugate was designed that can self-assemble into nanoparticles of around 70 nm with the efficiency of almost 100%. We introduced an Fmoc-peptide in the subsequent self-assembly step to stabilize the nanoparticles at physiological conditions. The two-component nanoparticles were demonstrated to be size-controllable within the range between 50 and 150 nm, stable upon incubation and dilution, well-tolerated by cells, and capable of encapsulating hydrophobic compounds. Moreover, the sequence of the Fmoc-peptide could be varied, within the design criteria that we have identified, to functionalize the particle surface with targeting moieties. As a particular application, we fabricated paclitaxel-loaded Fmoc-FRGD functionalized nanoparticles with an attractive loading capacity of around 50.9% compared to other systems (usually less than 30%) and a high encapsulation efficiency of around 98.6%. The drug-loaded nanoparticles showed better in vitro anticancer effects than free paclitaxel, with IC₅₀ value of about 3 nM against MDA-MB-435 breast carcinoma cells.

The design idea of the self-assembling systems may inspire the construction of additional functional nanomaterials using other aromatic moieties. The presented attractive characteristics of the two-component nanoparticles make them a promising novel drug delivery carrier for cancer therapy.