Selective elimination of macrophages by photodynamic therapy (PDT) is a new and promising therapeutic modality for the reduction of atherosclerotic plaques. m-Tetra(hydroxyphenyl)chlorin (mTHPC, or Temoporfin) may be suitable as photosensitizer for this application, as it is currently used in the clinic for cancer PDT. In the present study, mTHPC was encapsulated in polymeric micelles based on benzyl-poly(ε-caprolactone)-b-methoxy poly(ethylene glycol) (Ben-PCL-mPEG) using a film hydration method, with loading capacity of 17%. Because of higher lipase activity in RAW264.7 macrophages than in C166 endothelial cells, the former cells degraded the polymers faster, resulting in faster photosensitizer release and higher in vitro photocytotoxicity of mTHPC-loaded micelles in those macrophages. However, we observed release of mTHPC from the micelles in 30min in blood plasma in vitro which explains the observed similar in vivo pharmacokinetics of the mTHPC micellar formulation and free mTHPC. Therefore, we could not translate the beneficial macrophage selectivity from in vitro to in vivo. Nevertheless, we observed accumulation of mTHPC in atherosclerotic lesions of mice aorta's which is probably the result of binding to lipoproteins upon release from the micelles. Therefore, future experiments will be dedicated to increase the stability and thus allow accumulation of intact mTHPC-loaded Ben-PCL-mPEG micelles to macrophages of atherosclerotic lesions.

In this article, we show the great potential of dendrimers for driving the self-assembly of biohybrid protein nanoparticles. Dendrimers are periodically branched macromolecules with a perfectly defined and monodisperse structure. Moreover, they allow the possibility to incorporate functional units at predetermined sites, either at their core, branches, or surface. On these bases, we have designed and synthesized negatively charged phthalocyanine (Pc) dendrimers that behave as photosensitizers for the activation of molecular oxygen into singlet oxygen, one of the main reactive species in photodynamic therapy (PDT). The number of surface negative charges depends on dendrimer generation, whereas Pc aggregation can be tuned through the appropriate choice of the Pc metal center and its availability for axial substitution. Remarkably, both parameters determine the outcome and efficiency of the templated self-assembly process by which a virus protein forms 18 nm virus-like particles around these dendritic chromophores. Protein-dendrimer biohybrid nanoparticles of potential interest for therapeutic delivery purposes are obtained in this way. Biohybrid assemblies of this kind will have a central role in future nanomedical and nanotechnology applications.

This article describes a straightforward supramolecular strategy to encapsulate amphiphilic silicon phthalocyanines in polymeric micelles. A member of this new series of third-generation photosensitizers presents promising PDT activity.

A series of new metallodendrimers built around a ruthenium phthalocyanine core has been prepared. Employing a convergent synthetic strategy, pyridine-containing ligands were prepared and then assembled onto the ruthenium phthalocyanine through axial ligand coordination. The growing shell of oligoethylene glycol chains surrounding the lipophilic core allows solubilisation in water. Photophysical studies show that all the metallodendrimers are strongly phosphorescent and the deactivation pathway of their triplet state depends on the medium in which the compounds are dissolved. On one hand, quenching of the triplet state by the dendritic shell is observed and found to be substantially enhanced in aqueous media. On the other, the dendrimer shields the phthalocyanine from oxygen. This notwithstanding, the phthalocyanines are able to generate singlet oxygen in less polar environments such as in CHCl(3) or THF solution, while in water the generation of singlet oxygen is almost completely switched off.