Objectives: This review highlights both the physicochemical characteristics of the nanocarriers (NCs) and the physiological features of tumour microenvironment (TME) to outline what strategies undertaken to deliver the molecules of interest specifically to certain lesions. This review discusses these properties describing the convenient choice between passive and active targeting mechanisms with details, illustrated with examples of targeting agents up to preclinical research or clinical advances. Key findings: Targeted delivery approaches for anticancers have shown a steep rise over the past few decades. Though many successful preclinical trials, only few passive targeted nanocarriers are approved for clinical use and none of the active targeted nanoparticles. Herein, we review the principles and for both processes and the correlation with the tumour microenvironment. We also focus on the limitation and advantages of each systems regarding laboratory and industrial scale. Summary: The current literature discusses how the NCs and the enhanced permeation and retention effect impact the passive targeting. Whereas the active targeting relies on the ligand-receptor binding, which improves selective accumulation to targeted sites and thus discriminates between the diseased and healthy tissues. The latter could be achieved by targeting the endothelial cells, tumour cells, the acidic environment of cancers and nucleus.

Epigenetic silencing of tumor suppressor genes (TSGs) through DNA methylation and histone changes is a main hallmark of cancer. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a potent oncogene overexpressed in various solid and haematological tumors and its high expression levels are associated with decreased expression of several TSGs including p16 INK4A , BRCA1, PPARG and KiSS1. Using its several functional domains, UHRF1 creates a strong coordinated dialogue between DNA methylation and histone post-translation modification changes causing the epigenetic silencing of TSGs which allows cancer cells to escape apoptosis. To ensure the silencing of TSGs during cell division, UHRF1 recruits several enzymes including histone deacetylase 1 (HDAC1), DNA methyltransferase 1 (DNMT1) and histone lysine methyltransferases G9a and Suv39H1 to the right place at the right moment. Several in vitro and in vivo works have reported the direct implication of the epigenetic player UHRF1 in tumorigenesis through the repression of TSGs expression and suggested UHRF1 as a promising target for cancer treatment. This review describes the molecular mechanisms underlying UHRF1 regulation in cancer and discusses its importance as a therapeutic target to induce the reactivation of TSGs and subsequent apoptosis.

Nano-emulsions consist of stable suspensions of nano-scaled droplets that have huge loading capacities and are formulated with safe compounds. For these reasons, a large number of studies have described the potential uses of nano-emulsions, focusing on various aspects such as formulation processes, loading capabilities, and surface modifications. These studies typically concern direct nano-emulsions (i.e., oil-in-water), whereas studies on reverse nano-emulsions (i.e., water-in-oil) remain anecdotal. However, reverse nano-emulsion technology is very promising (e.g., as an alternative to liposome technology) for the development of drug delivery systems that encapsulate hydrophilic compounds within double droplets. The spontaneous emulsification process has the added advantages of optimization of the energetic yield, potential for industrial scale-up, improved loading capabilities, and preservation of fragile compounds targeted for encapsulation. In this study, we propose a detailed investigation of the processes and formulation parameters involved in the spontaneous nano-emulsification that produces water-in-oil nano-emulsions. The following details were addressed: (i) the order of mixing of the different compounds (method A and method B), (ii) mixing rates, (iii) amount of surfactants, (iv) type and mixture of surfactants, (v) amount of dispersed phase, and (vi) influence of the nature of the oil. The results emphasized the effects of the formulation parameters (e.g., the volume fraction of the dispersed phase, nature or concentration of surfactant, or nature of the oil) on the nature and properties of the nano-emulsions formed.

The treatment of cancer presents a clinical challenge both in human and veterinary medicine. Chemotherapy protocols require the use of toxic drugs that are not always specific, do not selectively target cancerous cells thus resulting in many side effects. A recent therapeutic approach takes advantage of the altered acidity of the tumour microenvironment by using proton pump inhibitors (PPIs) to block the hydrogen transport out of the cell. The alteration of the extracellular pH kills tumour cells, reverses drug resistance, and reduces cancer metastasis. Human clinical trials have prompted to consider this as a viable and safe option for the treatment of cancer in companion animals. Preliminary animal studies suggest that the same positive outcome could be achievable. The purpose of this review is to support investigations into the use of PPIs for cancer treatment cancer in companion animals by considering the evidence available in both human and veterinary medicine.

With a predicted 382.4 per 100,000 people expected to suffer from some form of malignant neoplasm by 2015, and a current death toll of 1 out of 8 deaths worldwide, improving treatment and/or drug design is an essential focus of cancer research. Multi-drug resistance is the leading cause of chemotherapeutic failure, and delivery of anticancer drugs to the inside of cancerous cells is another major challenge. Fifteen years ago, in a completely different field in which improving drug delivery is the objective, the bioavailability of oral compounds, Christopher Lipinski formulated some rules that are still used by the pharmaceutical industry as rules of thumb to improve drug delivery to their target. Although Lipinski’s rules were not formulated to improve delivery of antineoplastic drugs to the inside of cancer cells, it is interesting to note that the problems are similar. On the basis of the strong similarity between the fields, we discuss how they can be connected and how new drug targets can be defined in cancer.