Francesca Gorini

Hierarchical paclitaxel encapsulation in microbead-embedded microparticles for sustained ovarian cancer therapy.

Ovarian cancer (OC) is the most lethal gynecologic malignancy, often diagnosed at advanced stages due to clinically silent peritoneal carcinomatosis. Although intraperitoneal (IP) chemotherapy enhances drug exposure, its effectiveness is hindered by rapid clearance, toxicity, and uneven distribution. To address these challenges, we developed a novel drug delivery system integrating paclitaxel (PTX)-loaded poly(lactic-co-glycolic acid) microparticles (PLGA-MPs) within calcium-alginate microbeads (Alg-MBs). This system aims to provide sustained drug release while minimizing adverse effects. PTX-loaded PLGA-MPs were prepared via solvent evaporation and encapsulated in Alg-MBs using a coaxial air jet generator. In vitro studies showed an initial burst release over five days, followed by sustained release until day 21, confirming the role of Alg-MBs in modulating drug diffusion. Cytotoxicity tests in 2D SKOV-3 OC cultures revealed dose-dependent effects, with increased PTX concentrations reducing cell viability. A 3D bioprinted tumor model was used to better replicate in vivo conditions and evaluate long-term efficacy. Sustained PTX release resulted in progressive tumor cell death over 21 days, with delayed but potent cytotoxicity at higher doses. These findings support hierarchical PTX microencapsulation for prolonged IP chemotherapy, while the 3D bioprinted model provided a more physiologically relevant platform for evaluating long-term therapeutic efficacy in OC treatment.

miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy

AbstractEndometrial cancer (EC) is the most prevalent gynecological cancer in high‐income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity‐related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; ≥30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI ≥30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI ≥30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR‐199a‐5p, miR‐449a, miR‐449b‐5p) in normal‐weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity‐related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity‐related pathways and that may provide novel implications for the clinical management of obese EC patients.