Control of cell penetration enhancer shielding and endosomal escape-kinetics crucial for efficient and biocompatible siRNA delivery.

Although cationic liposomes are efficient carriers for nucleic acid delivery, their toxicity often hampers the clinical translation. Polyethylene glycol (PEG) coating has been largely used to improve their stability and reduce toxicity. Nevertheless, it has been found to decrease the transfection process.

When drug nanocarriers miss their target: extracellular diffusion and cell uptake are not enough to be effective.

Biocompatible nanoscale iron carboxylate metal-organic frameworks (nanoMOFs) have already demonstrated their ability to efficiently deliver various therapeutic molecules. The versatility of the synthesis methods and functionalization strategies could further improve their drug carrier potential. However, in oncology, preclinical evaluation still suffers from the lack of relevant models able to mimic the heterogeneity and the microenvironment of human tumors.

Screening of chemical linkers for development of pullulan bioconjugates for intravitreal ocular applications.

The treatment of posterior segment disorders of the eye requires therapeutic strategies to achieve drug effects over prolonged times. Innovative colloidal delivery systems can be designed to deliver drugs to the retina and prolong their intravitreal permanence. In order to exploit pullulan (Pull) as polymeric drug carrier for intravitreal drug delivery, derivatives of hydrophobic model molecule rhodamine B (RhB) were conjugated to the pullulan backbone through linkers with different stability, namely ether (Et), hydrazone (Hy) or ester (Es) bond to obtain Pull-Et-RhB, Pull-Hy-RhB and Pull-Es-RhB, respectively.

Light sheet fluorescence microscopy versus confocal microscopy: in quest of a suitable tool to assess drug and nanomedicine penetration into multicellular tumor spheroids.

We recently constructed a multicellular spheroid model of pancreatic tumor based on a triple co-culture of cancer cells, fibroblasts and endothelial cells and characterized by the presence of fibronectin, an important component of the tumor extracellular matrix. By combining cancer cells and stromal components, this model recreates in vitro the three-dimensional (3D) architecture of solid tumors. In this study, we used these hetero-type spheroids as a tool to assess the penetration of doxorubicin (used as a model drug) through the whole tumor mass either in a free form or loaded into polymer nanoparticles (NPs), and we investigated whether microscopy images, acquired by Confocal Laser Scanning Microscopy (CLSM) and Light Sheet Fluorescence Microscopy (LSFM), would be best to provide reliable information on this process.