Encapsulation of a TRPM8 Agonist, WS12, in Lipid Nanocapsules Potentiates PC3 Prostate Cancer Cell Migration Inhibition through Channel Activation.

In prostate carcinogenesis, expression and/or activation of the Transient Receptor Potential Melastatin 8 channel (TRPM8) was shown to block in vitro Prostate Cancer (PCa) cell migration. Because of their localization at the plasma membrane, ion channels, such as TRPM8 and other membrane receptors, are promising pharmacological targets. The aim of this study was thus to use nanocarriers encapsulating a TRPM8 agonist to efficiently activate the channel and therefore arrest PCa cell migration. To achieve this goal, the most efficient TRPM8 agonist, WS12, was encapsulated into Lipid NanoCapsules (LNC). The effect of the nanocarriers on channel activity and cellular physiological processes, such as cell viability and migration, were evaluated in vitro and in vivo. These results provide a proof-of-concept support for using TRPM8 channel-targeting nanotechnologies based on LNC to develop more effective methods inhibiting PCa cell migration in zebrafish xenograft.

Balancing nanotoxicity and returns in health applications: The Prisoner's Dilemma.

Over the past 30 years, there have been significant advancements in the field of nanomaterials. The possibility to use them in applications such as cancer treatment is extremely promising; however, the toxicity of many nanomaterials as well as the high costs associated with their use is still a concern. This paper aims to study the connection between nanomaterial toxicity and cost. This synergy may be interpreted as a different version of the classic "Prisoner's Dilemma" game, which in this case attempts to explain the possible outcomes of cooperation versus conflict between science advocating for the use of high-risk, possibly toxic materials due to their high returns, and society that might be dubious about the use of high-risk materials. In an effort to create diverse evaluation methodologies, this work uses a forecast horizon to evaluate the current status and expected future of the nanomaterials market. The historical progress of each market, toxicity information, and possible returns stemming from their use is taken into account to analyze the predictions. Our results suggest various trends for the associated costs and nanotoxicity of the studied materials.

Kidney stone nano-structure - Is there an opportunity for nanomedicine development?

BACKGROUND: Kidney stone analysis techniques are well-established in the field of materials characterization and provide information for the chemical composition and structure of a sample. Nanomedicine, on the other hand, is a field with an increasing rate of scientific research, a big budget and increasingly developing market. The key scientific question is if there is a possibility for the development of a nanomedicine to treat kidney stones. MAJOR CONCLUSIONS: The main calculi characterization techniques such as X-ray Diffraction and Fourier Transform Infrared Spectroscopy can provide information about the composition of a kidney stone but not for its nanostructure. On the other hand, Small Angle X-ray Scattering and Nitrogen Porosimetry can show the nanostructural parameters of the calculi. The combination of the previously described parameters can be used for the development of nano-drugs for the treatment of urolithiasis, while no such nano-drugs exist yet. GENERAL SIGNIFICANCE: In this study, we focus on the most well-known techniques for kidney stone analysis, the urolithiasis management and the search for possible nanomedicine for the treatment of kidney stone disease. We combine the results from five different analysis techniques in order to represent a three dimensional model and we propose a hypothetical nano-drug with gold nanoparticles. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

A framework for health-related nanomaterial grouping.

BACKGROUND: Nanotechnology has been in the limelight since its emergence and its products affect everyday lives. Nanomaterials are characterized by features such as size and shape, thus rendering their possible number essentially unlimited, which in turn makes them difficult to study and categorize regarding possible dangers. This work suggests that grouping could allow studying them with limited testing efforts without endangering safety. METHODS: Initially, the materials are identified and grouped according to their applications in health/medicine, as well as on their environmentally-friendly potential. The materials are then categorized using various toxicity classification methods to identify those with highest risks and group them with others that demonstrate similar behavior. RESULTS: The materials studied show promising uses in diagnostics, drug delivery, biosensors, water purification, oil spill cleaning, emission control and other fields. The toxicity risk assessment shows that the majority pose little to moderate risk, however there are certain materials that can be extremely hazardous or even cause death under specific circumstances. A risk mitigation plan was also developed. CONCLUSIONS: Nanomaterials applications, including drug delivery, cancer treatment, waste treatment, solar energy generation etc. can be very beneficiary, but at the same time, these materials can be extremely harmful or even cause death, thus making the need to prioritize research on high risk materials crucial. A clear regulatory framework that addresses both benefits and risks and communicates that information effectively should play an important part in European and worldwide efforts. GENERAL SIGNIFICANCE: The risk analysis validated the impression that there is limited research on nanomaterial toxicity risks, which calls for a more organized approach. The framework outlined in this work can be utilized by researchers as well as government bodies, in order to form regulatory policies and adopt a universally accepted labeling system. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression.

Although the transient receptor potential melastatin 8 (TRPM8) cold receptor is highly expressed in prostate cancer (PCa) and constitutes a promising diagnostic and prognostic indicator, the natural agonists of this channel in the prostate, as well as its physiological and pathological functions, remain unknown. In this study, we identified the well-known PCa marker, prostate-specific antigen (PSA), as a physiological TRPM8 agonist. Electrophysiological and Ca(2+) imaging studies demonstrated that PSA activated TRPM8-mediated current by the bradykinin 2 receptor signaling pathway. Further investigation of this mechanism by cell-surface biotinylation revealed that the increase in TRPM8 current induced by PSA was due to an increase in the number of functional TRPM8 channels on the plasma membrane. Importantly, wound-healing and migration assays revealed that TRPM8 activation by PSA reduced motility of the PC3 PCa cell line, suggesting that plasma membrane TRPM8 has a protective role in PCa progression. Consequently, PSA was identified as a natural TRPM8 agonist in the prostate and we propose a putative physiological role for both of these proteins in carcinogenesis, making this pathway a potentially important target for anticancer agent development.