Molecular Nanoparticles and GelsMaterials for Biomedical and Photonic Applications

Resumen

The general objective of the present thesis is the study and development of low molecular weight gelators with photonic and biomedical applications. The thesis is divided in five sections as follows: Orthogonal fibrillization resulting in gel formation of photoactive compounds is reported. A very efficient EET between complementary fluorophores, acridine and 4-amino-1,8-naphthalimide, has been shown. The system described here differs from previously reported related cases in that fibrillization of both donor and acceptor is a requisite for the light manipulation. This fact together with the reversible nature of molecular gels affords tunable photonic soft materials. Aggregation induced emission (AIE) in several derivatives of 1,8-naphthalimide moiety has been studied. Some of the derivatives form molecular hydrogels that self-organize in sample-spanning networks. As far as we know observation of such strong AIE in self-assembled gels of 1,8-naphtalimide derivatives in aqueous media is unprecedented (Φf = 30 %) and opens the way for biomedical related applications. Besides, It is observed that the fibrillar assembly is associated to AIE with emission at ca. 405 nm reading a remarkable enhancement of the fluorescence intensity of 4700% Notably, compounds showing non-fibrillar aggregation also experience AIE but emission is shifted to ca. 460 nm, which can be ascribed to excimer formation. Therefore, the aggregation mode modulates the wavelength of the emitted light. Miniaturization of macroscopic molecular gels into molecular nano- and microgels and the ability of these molecular particles to load and release actives, as well as act as intracellular carriers was demonstrated as proof of concept. The stimuli-responsiveness of the nanogels was investigated, showing relatively size insensitivity to temperature, dilution and salt content. Molecular microgels were also synthesized in this way by precipitation method and its loading and release abilities were investigated showing high loading capacity of different dyes and photosensitizers that in turn, has been used, tentatively, as in vitro photodynamic therapy agent. New hybrid systems, combining supramolecular photonic gels of naphthalimide derivatives and upconverting NaYF4:Yb/Tm nanoparticles (UCNPs), have been prepared. The hybrid system reversibly, manipulates light as a result of an optical communication between the UCNPs and the photoactive gel network. Moreover, synthesis of a new hybrid nanomaterial, which can be suspended in water (Dye+UCNP@1 NGs), was developed with the idea of applying it in photodynamic therapy in deep tissues. Good dispersion and stabilization of oleic acid coated core-shell UCNPs was achieved by incorporation into organic nanoparticles (nanogels). The singlet oxygen production upon IR irradiation confirmed the energy transfer process and reveals very interesting potential uses as photodynamic agents. The aggregation in aqueous media 4-amino-1,8-naphthalimide (ANI) derivatives, and their reactivity towards dissolved nitric oxide in aerated medium have been studied. It has been found that the ANI fluorophore experiences deamination upon exposure to NO in aerated aqueous systems, with the concomitant fluorescence turn-off process. This deamination mechanism is found to be dependent on the architecture of the molecule and its supramolecular organization. Systems with tendency to form self-assembled structures which orientate the reactive amine towards the aqueous solvent, display an attenuated reactivity. Others are completely insensitive, that is de case of those whose reactive amine is completely buried inside hydrophobic regions.