The Balance Between Shear Flow and Extracellular Matrix in Ovarian Cancer-on-Chip.

Ovarian cancer is the most lethal gynecologic cancer in developed countries. In the tumor microenvironment, the extracellular matrix (ECM) and flow shear stress are key players in directing ovarian cancer cells invasion. Artificial ECM models based only on ECM proteins are used to build an ovarian tumor-on-chip to decipher the crosstalk between ECM and shear stress on the migratory behavior and cellular heterogeneity of ovarian tumor cells. This work shows that in the shear stress regime of the peritoneal cavity, the ECM plays a major role in driving individual or collective ovarian tumor cells migration. In the presence of basement membrane proteins, migration is more collective than on type I collagen regardless of shear stress. With increasing shear stress, individual cell migration is enhanced; while, no significant impact on collective migration is measured. This highlights the central position that ECM and flow shear stress should hold in in vitro ovarian cancer models to deepen understanding of cellular responses and improve development of ovarian cancer therapeutic platforms. In this frame, adding flow provides significant improvement in biological relevance over the authors' previous work. Further steps for enhanced clinical relevance require not only multiple cell lines but also patient-derived cells and sera.

In Vitro Models of Ovarian Cancer: Bridging the Gap between Pathophysiology and Mechanistic Models.

Ovarian cancer (OC) is a disease of major concern with a survival rate of about 40% at five years. This is attributed to the lack of visible and reliable symptoms during the onset of the disease, which leads over 80% of patients to be diagnosed at advanced stages. This implies that metastatic activity has advanced to the peritoneal cavity. It is associated with both genetic and phenotypic heterogeneity, which considerably increase the risks of relapse and reduce the survival rate. To understand ovarian cancer pathophysiology and strengthen the ability for drug screening, further development of relevant in vitro models that recapitulate the complexity of OC microenvironment and dynamics of OC cell population is required. In this line, the recent advances of tridimensional (3D) cell culture and microfluidics have allowed the development of highly innovative models that could bridge the gap between pathophysiology and mechanistic models for clinical research. This review first describes the pathophysiology of OC before detailing the engineering strategies developed to recapitulate those main biological features.

Current knowledge on the tissue distribution of mRNA nanocarriers for therapeutic protein expression.

Exogenously delivered mRNA-based drugs are emerging as a new class of therapeutics with the potential to treat several diseases. Over the last decade, advancements in the design of non-viral delivery tools have enabled mRNA to be evaluated for several therapeutic purposes including protein replacement therapies, gene editing, and vaccines. However, in vivo delivery of mRNA to targeted organs and cells remains a critical challenge. Evaluation of the biodistribution of mRNA vehicles is of utmost importance for the development of effective pharmaceutical candidates. In this review, we discuss the recent advances in the design of nanoparticles loaded with mRNA and extrapolate the key factors influencing their biodistribution following administration. Finally, we highlight the latest developments in the preclinical and clinical translation of mRNA therapeutics for protein supplementation therapy.

Mechanofluorochromic Difluoroboron ß-Diketonates Based Polymer Composites: Toward Multi-Stimuli Responsive Mechanical Stress Probes.

Developing mechano-responsive fluorescent polymers that exhibit distinct responses to distinct mechanical stresses requires a careful design of the fluorophore in order to tune its interactions with the polymer. A series of mechanofluorochromic (MFC) polymer composites are prepared by dispersing difluoroboron diketonates complexes with various alkyl side-chain lengths (DFB-alkyl) in linear low-density polyethylene. Observation of the resulting polymer composites under a microscope reveals different aggregate sizes of the three DFB-alkyls, thus confirming the functionalization by alkyl side chains as a powerful approach to control the aggregation process in a polymer. Besides, the three polymer composite samples are shown to be sensitive to both stretching and scratching, thereby consisting in the first reported example of MFC polymer responding to these two distinct mechanical stimuli. To establish a structure-property relationship, the strategy consisted in applying controlled tensile or friction forces while simultaneously monitoring fluorescence changes. Interestingly, the intensity of the MFC response to both stretching and scratching depends on the alkyl chain length and thus on the aggregation properties of the fluorophore. According to a time-resolved fluorescence study, the emission is found to originate from different species following the type of applied stress (tensile or friction force).