Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells.

RNA interference (RNAi), a natural cellular mechanism for RNA-guided regulation of gene expression could in fact become new therapeutic modality if an appropriate efficient delivery strategy that is also reproducible and safe will be developed. Numerous efforts have been made for the past eight years to address this challenge with only mild success. The majority of these strategies are based on cationic formulations that condense the RNAi payload and deliver it into the cell cytoplasm. However, most of these formulations also evoke adverse effects such as mitochondrial damage, interfering with blood coagulation cascade, induce interferon response, promote cytokine induction and activate the complement. Herein, we present a strategy that is devised from neutral phospholipids and cholesterol that self-assembled into lipid-based nanoparticles (LNPs). These LNPs were then coated with the glycosaminoglycan, hyaluronan (HA). HA-LNPs bound and internalized specifically into cancer cells compared with control, non-coated particles. Next, loaded with siRNAs against the multidrug resistance extrusion pump, p-glycoprotein (P-gp), HA-LNPs efficiently and specifically reduced mRNA and P-gp protein levels compared with control particles and with HA-LNPs loaded with control, non-targeted siRNAs. In addition, no cellular toxicity or cytokine induction was observed when these particles were cultured with human Peripheral Blood Mononuclear Cells (PBMCs). The HA-LNPs may offer an alternative approach to cationic lipid-based formulations for RNAi delivery into cancer cells in an efficient and safe manner.

Pulmonary thrombosis in the mouse following intravenous administration of quantum dot-labeled mesenchymal cells.

Quantum dots (QDs) are emerging as novel diagnostic agents. Yet, only a few studies have examined the possible deleterious effects of QD-labeled stem cells. We assessed the potential toxic effects of QD-labeled human embryonic palatal mesenchymal (QD-HEPM) cells in male NOD/SCID mice for six months, following the administration of a single intravenous injection. Control animals were administered with non-labeled HEPM cells. No treatment-related clinical signs, hematological, or biochemical parameters were found in the QD-HEPM animals in comparison to control animals. Histologically, multifocal organizing thrombi were noted in the pulmonary arteries of all QD-HEPM animals from the one-week study group and in one animal from the one-month group. Additionally, increased severity of perivascular inflammation was noted at the injection sites of QD-HEPM animals from the one-week group. This is the first study reporting histopathological evidence for pro-thrombotic adverse effects mediated by QD labeling.