Stimuli-Responsive Nanoparticles for Bio-Applications

Stimuli-responsive nanoparticles have been designed and studied, exploring their potentiality as self-assembled materials as building blocks for the development of "smart" materials for bio-applications. Perylene diimide derivatives (PDI) have been used as fluorogenic units and structural components of assembled high-brightness nanoparticles, where fluorescence changes can be triggered by external (light) or internal (pH) stimuli which promote disaggregation induced emission (DIE). Synthesis of PDI (P) was achieved by microwave heating in mild conditions. π-π stacking and inter-substituent interactions drove the self-assembly of quenched nanoparticles that were internalized by yeast cells responding as fluorogenic imaging agents. By controlling the dosage, they displayed either green or red fluorescence. Multicolour fluorescence imaging was achieved by sample photo-activation under strong light irradiation. P was adopted as structural component of covalently linked nanoparticles. P chains have been cross-linked by an epoxy monomer into Pluronic micelles, driving the formation of core-shell nanoparticles. Vicinity of the monomer aromatic regions caused the quenching of the emission, which could be recovered by fluorophore disaggregation triggered by light irradiation in proper conditions of concentration and/or polarity. Photo-activation occurred also after nanoparticles internalization by living cells, confirming the possibility of using them as stimuli-responsive fluorogenic bio-imaging agents. Fluorogenic pH-responsive nanoparticles have been further designed and developed, with the purpose of differentiate normal and cancer tissues. A monodispersed amphiphilic block co-polymer, constituted by a PEGylated hydrophilic block and a tertiary amine pH responsive hydrophobic block, functionalized by a PDI norbornene monomer, was synthesised by ring opening metathesis polymerization. Polymer self-assembly was exploited to obtain spherical core-shell nanoparticles, quenched in neutral pH thanks to the π-π stacking in the nanoparticles core. By switching the pH from 7.4 to 5, structural modification in the hydrophobic block were promoted, leading to the nanoparticles disassembly and to the recovery of PDI emission.