Ferrocifen stealth LNCs and conventional chemotherapy: A promising combination against multidrug-resistant ovarian adenocarcinoma.

Ovarian cancer is one of the deadliest epithelial malignancies in women, owing to the multidrug resistance that restricts the success of conventional chemotherapy, carboplatin and paclitaxel. High grade serous ovarian carcinoma can be classified into two subtypes, the chemosensitive High OXPHOS and the Low OXPHOS tumour, less sensitive to chemotherapy. This difference of treatment efficacy could be explained by the redox status of these tumours, High OXPHOS exhibiting a chronic oxidative stress and an accumulation of reactive oxygen species. Ferrocifens, bio-organometallic compounds, are believed to be ROS producers with a good cytotoxicity on ovarian cancer cell lines. The aim of this study was to evaluate the in vivo efficacy of ferrocifen stealth lipid nanocapsules on High and Low OXPHOS ovarian Patient-Derived Xenograft models, alone or in combination to standard chemotherapy. Accordingly, two ferrocifens, P53 and P722, were encapsulated in stealth LNCs. The treatment by stealth P722-LNCs in combination with standard chemotherapy induced, with a concentration eight time lower than in stealth P53-LNCs, similar tumour reduction on a Low OXPHOS model, allowing us to conclude that P722 could be a leading ferrocifen to treat ovarian cancer. This combination of treatments may represent a promising synergistic approach to treat resistant ovarian adenocarcinoma.

Microbiota and nanoparticles: Description and interactions.

The healthy human body is inhabited with a large number of bacteria, forming natural flora. It is even estimated that for a human body, its amount of DNA is less important that its bacterial genetic material. This flora plays major roles in the sickness and health of the human body and any change in its composition may lead to different diseases. Nanoparticles are widely used in numerous fields: cosmetics, food, industry, and as drug delivery carrier in the medical field. Being included in these various applications, nanoparticles may interact with the human body at various levels and with different mechanisms. These interactions differ depending on the nanoparticle nature, its structure, its concentration and manifest in different ways on the microbiota, leading to its destabilization, its restoring or showing no toxic effect. Nanoparticles may also be used as a vehicle to regulate the microbiota or to treat some of its diseases.

Microbiota and cancer: In vitro and in vivo models to evaluate nanomedicines.

Nanomedicine implication in cancer treatment and diagnosis studies witness huge attention, especially with the promising results obtained in preclinical studies. Despite this, only few nanomedicines succeeded to pass clinical phase. The human microbiota plays obvious roles in cancer development. Nanoparticles have been successfully used to modulate human microbiota and notably tumor associated microbiota. Taking the microbiota involvement under consideration when testing nanomedicines for cancer treatment might be a way to improve the poor translation from preclinical to clinical trials. Co-culture models of bacteria and cancer cells, as well as animal cancer-microbiota models offer a better representation for the tumor microenvironment and so potentially better platforms to test nanomedicine efficacy in cancer treatment. These models would allow closer representation of human cancer and might smoothen the passage from preclinical to clinical cancer studies for nanomedicine efficacy.

Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis*.

Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene-containing (Fc-CH2 -OXA), ruthenocene-containing (Rc-CH2 -OXA) and benzene-containing (Ph-CH2 -OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both Schistosoma mansoni larvae and adult worms and S. haematobium adult worms, and were also active in vivo against adult S. mansoni. Encouraged by these promising results, we conducted additional in-depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on S. haematobium and juvenile S. mansoni, computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on S. haematobium. This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.