Isothiocyanate-Functionalized Mesoporous Silica Nanoparticles as Building Blocks for the Design of Nanovehicles with Optimized Drug Release Profile.

A straightforward methodology for the synthesis of isothiocyanate-functionalized mesoporous silica nanoparticles (MSNs) by exposure of aminated MSNs to 1,1'-thiocarbonyldi-2(1H)-pyridone is reported. These nanoparticles are chemically stable, water tolerant, and readily react with primary amines without the formation of any by-product. This feature allows the easy modification of the surface of the nanoparticles for tuning their physical properties and the introduction of gatekeepers on the pore outlets. As a proof-of-concept, amino-isothiocyanate-functionalized MSNs have been used for the design of a nanocontainer able to release the drug Ataluren. The release profile of the drug can be easily fine-tuned with the careful choice of the capping amine.

Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery.

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide-polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.

Modifications of microvascular EC surface modulate phototoxicity of a porphycene anti-ICAM-1 immunoconjugate; therapeutic implications.

Inflammation and shear stress can upregulate expression of cellular adhesion molecules in endothelial cells (EC). The modified EC surface becomes a mediating interface between the circulating blood elements and the endothelium, and grants opportunity for immunotherapy. In photodynamic therapy (PDT), immunotargeting might overcome the lack of selectivity of currently used sensitizers. In this study, we hypothesized that differential ICAM-1 expression modulates the effects of a drug targeted to surface ICAM-1. A novel porphycene-anti-ICAM-1 conjugate was synthesized and applied to treat endothelial cells from macro and microvasculature. Results show that the conjugate induces phototoxicity in inflamed, but not in healthy, microvascular EC. Conversely, macrovascular EC exhibited phototoxicity regardless of their state. These findings have two major implications; the relevance of ICAM-1 as a modulator of drug effects in microvasculature, and the potential of the porphycene bioconjugate as a promising novel PDT agent.