Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and biodistribution improvements.

Malignant melanoma is an aggressive tumor, associated with the presence of local and/or distant metastases. The development of gene therapy by the use of small interfering RNA (siRNA) represents a promising new treatment. However, the protection of this biomolecule is necessary in order for it to be intravenously administrated, for example its incorporation into nanomedicines.

Melanoma tumour vasculature heterogeneity: from mice models to human.

Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients.

Efficient ferrocifen anticancer drug and Bcl-2 gene therapy using lipid nanocapsules on human melanoma xenograft in mouse.

Metastatic melanoma has been described as a highly aggressive cancer with low sensibility to chemotherapeutic agents. New types of drug, such as metal-based drugs (ferrocifens) have emerged and could represent an alternative for melanoma treatment since they show interesting anticancer potential. Furthermore, molecular analysis has evidenced the role of apoptosis in the low sensibility of melanomas and especially of the key regulator, Bcl-2.

Challenges and Successes Using Nanomedicines for Aerosol Delivery to the Airways.

Numerous diseases affect the respiratory tract and the aerosol administration has been widely considered as an adapted and non-invasive method for local delivery. This pathway induces a lung concentration and thus also limits, systemic side effects. However, aerosol delivery of active pharmaceutical ingredients represents a real challenge, due to numerous obstacles such as the specific respiratory movement, the presence of mucus or surfactant, and the mucociliary clearance.

Characterization and comparison of two novel nanosystems associated with siRNA for cellular therapy.

To direct stem cell fate, a delicate control of gene expression through small interference RNA (siRNA) is emerging as a new and safe promising strategy. In this way, the expression of proteins hindering neuronal commitment may be transiently inhibited thus driving differentiation. Mesenchymal stem cells (MSC), which secrete tissue repair factors, possess immunomodulatory properties and may differentiate towards the neuronal lineage, are a promising cell source for cell therapy studies in the central nervous system.

Efficient in vitro gene therapy with PEG siRNA lipid nanocapsules for passive targeting strategy in melanoma.

Small interfering RNA (siRNA)-mediated gene therapy is a promising strategy to temporarily inhibit the expression of proteins implicated in carcinogenesis or chemotherapy resistance. Although intra-tumoral administration can be envisaged, studies currently focus on formulating nanomedicines for intravenous injection to target tumor sites as well as metastases. The development of synthetic nanoparticles and liposomes has advanced greatly during the last decade.

A review of the current status of siRNA nanomedicines in the treatment of cancer.

RNA interference currently offers new opportunities for gene therapy by the specific extinction of targeted gene(s) in cancer diseases. However, the main challenge for nucleic acid delivery still remains its efficacy through intravenous administration. Over the last decade, many delivery systems have been developed and optimized to encapsulate siRNA and to specifically promote their delivery into tumor cells and improve their pharmacokinetics for anti-cancer purposes.

EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro.

Glioma are the most common malignant tumors of the central nervous system and remain associated with poor prognosis, despite the combination of chemotherapy and radiotherapy. EGFR targeting represents an interesting strategy to treat glioma. Indeed, a high level of endothelial growth factor receptors expression (EGFR), involved in the malignancy of the tumor, has been observed in glioma.

Treatment efficacy of DNA lipid nanocapsules and DNA multimodular systems after systemic administration in a human glioma model.

Background: We previously developed different types of DNA nanocarriers for systemic administration. Recently, the biodistribution profiles of these intravenously administered nanocarriers, DNA lipid nanocapsules (LNCs) and different multimodular systems (MMS), were analysed in healthy mice using in vivo biofluorescence imaging.

Methods: In the present study, the experiments were performed in an ectopic human U87MG glioma model in nude mice.

siRNA LNCs--a novel platform of lipid nanocapsules for systemic siRNA administration.

Several siRNA (small interfering RNA) therapeutics are undergoing clinical trials for cancer, respiratory diseases or macular degeneration, but most are administrated locally. In order to overcome the different barriers to attain an efficient siRNA action after systemic administration, nanocarriers able to carry and protect siRNA are awaited. With this aim, we developed a new platform of siRNA lipid nanocapsules (LNCs) using different cationic lipids, combining the properties of LNCs (siRNA protection and targeting) and lipoplexes (efficient siRNA delivery into the cell).

In vivo imaging of DNA lipid nanocapsules after systemic administration in a melanoma mouse model.

The biodistribution of intravenously injected DNA lipid nanocapsules (DNA LNCs), encapsulating pHSV-tk, was analysed by in vivo imaging on an orthotopic melanoma mouse model and by a subsequent treatment with ganciclovir (GCV), using the gene-directed enzyme prodrug therapy (GDEPT) approach. Luminescent melanoma cells, implanted subcutaneously in the right flank of the mice, allowed us to follow tumour growth and tumour localisation with in vivo bioluminescence imaging (BLI). In parallel, DNA LNCs or PEG DNA LNCs (DNA LNCs recovered with PEG(2000)) encapsulating a fluorescent probe, DiD, allowed us to follow their biodistribution with in vivo biofluorescence imaging (BFI).