Background: Thyroid cancer (TC) is the most prevalent endocrine malignancy, and is categorized into well-differentiated and aggressive anaplastic types. Novel therapeutic modalities are needed for TC. Nanomedicine is a promising strategy for the development of precision medicine. In this context, we investigated the use of nanogels (NGs) to deliver agents with different physicochemical properties, specifically the hydrophilic agent doxorubicin (DOX) and the hydrophobic compound curcumin (CUR), in TC cell lines. Methods: Nα-9-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) peptide-based NGs loaded with DOX and CUR were formulated using the solvent-switch method. DOX-loaded NGs were previously characterized. CUR-loaded NGs were characterized through rheology, scanning electron microscopy (SEM), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and Fourier transform infrared (FT-IR) spectroscopy. Confocal microscopy, q-RT-PCR, and ATP lite assays were performed to evaluate the uptake and delivery of DOX- and CUR-loaded NGs on TC cell lines. Results: CUR-loaded NGs exhibited a mean diameter of approximately 204.3 nm and a zeta potential of −34.6 mV, indicative of a good stability. In vitro release studies revealed a sustained release profile of CUR over 72 h. Functional analyses demonstrated that Fmoc-FF-loaded NGs were internalized into TC cell lines. They were primarily localized in the cytoplasm rather than in early endosomes, thereby ensuring intracellular stability. Furthermore, Fmoc-FF NGs reduced the nuclear uptake kinetics of DOX in TC cells, suggesting a potential reduction in dose-limiting toxicity. Comparative studies with CUR-loaded NGs revealed similar internalization and delayed nuclear uptake, highlighting the efficacy of Fmoc-FF NGs in delivering hydrophobic agents. Conclusions: Overall, the data suggest that Fmoc-FF NGs represent a promising strategy for delivering agents with diverse physicochemical properties in TC, enhancing their efficacy and safety and warranting further investigation.

During tumorigenesis, miRNAs with unbalanced expression profiles can increase the threat of disease progression. Here, we focus on the role of miR-331-5p in the pathogenesis of thyroid cancer (TC). In vitro studies were conducted using TC cell lines after the forced expression and silencing of miR-331-5p. Cell proliferation and viability were analyzed via cell counts and colorimetric assays. Cell motility was analyzed via wound healing assays, Transwell migration and invasion assays, and Matrigel Matrix assays. The putative targets of miR-331-5p were unveiled via label-free proteomic screening and then verified using Western blot and luciferase assays. Expression studies were conducted by interrogating The Cancer Genome Atlas (TCGA). We found that ectopic miR-331-5p expression reduces TC cell motility, while miR-331-5p silencing induces the opposite phenotype. Proteomic screening revealed eight putative downregulated targets of miR-331-5p, among which BID was confirmed as a direct target. TCGA data showed the downregulation of miR-331-5p and the upregulation of BID in TC tissues. In summary, deregulation of the miR-331-5p/BID axis could enhance the aggressiveness of TC cell lines, providing new insights into the mechanisms of the progression of this disease and suggesting a potential role of the component factors as possible biomarkers in TC tissues.

Since cancer-related miRNAs expression are affected by physical activity/exercise, they represent an attractive tool to monitor this response in healthy and in cancer subjects. Here, we aim to update the literature regarding the benefit of this axis in oncology field. We systematically questioned the literature according to PRISMA guidelines defining our questions by PICO tool and carrying out the risk of bias and quality assessment by NOS. Among 751 records risen from the initial search, 28 studies resulted eligible. The majority of studies regarded breast cancer, while others were initially conducted in healthy subjects and afterwards authors speculated on the relationship between exercise-modulated miRNAs and cancer. Physical activity/exercise induces beneficial effects in the cancer prevention, prognosis and treatments. Among the miRNAs modulated by physical activity/exercise, miR-21, let-7 and miR-133 families resulted the most promising in this field.

Among the non-coding RNAs, the aberrant expression of microRNAs (miRNAs) is well described in the oncology field. It is clear that the altered expression of miRNAs is crucial for a variety of processes such as proliferation, apoptosis, motility, angiogenesis and metastasis insurgence. Considering these aspects, RNA-based therapies and the use of miRNAs as non-invasive biomarkers for early diagnosis are underlined as promising opportunities against cancer death. In the era of precision medicine, significant progress in next-generation sequencing (NGS) techniques has broadened knowledge regarding the miRNAs expression profile in cancer tissues and in the blood of cancer patients. In this scenario, pre-clinical and clinical studies suggested that the members of the miR-584 family, i.e., miR-584-5p and -3p, are prominent players in cancer development and progression. Under some conditions, these miRNAs are under-expressed in cancer tissues acting as tumor suppressors, while in other conditions, they are overexpressed, acting as oncogenes increasing the aggressive behavior of cancer cells. The aim of this review is to provide a comprehensive and up-to-date overview on the expression, upstream genes, molecular targets and signaling pathways influenced by the miR-584 family (i.e., miR-584-3p and -5p) in various human solid and hematological cancers. To achieve this goal, 64 articles on this topic are discussed. Among these articles, 55 are focused on miR-584-5p, and it is outlined how this miRNA could be used in future applications as a potential new therapeutic strategy and diagnostic tool.

Increasing evidence revealed that restoring the correct expression of lncRNAs could have implications in the management of melanoma patients. In this context, here, we aim to dissect the main characteristics of lncRNAs altered in melanoma and their crosstalk with the signaling pathways involved in the progression of this disease. We also highlight the role of nucleic acid-based techniques and natural compounds (i.e., phytochemicals) as a therapeutic tool to increase or silence their expression in cancer cells. Finally, we explore the advances in nanotechnologies as delivery systems to efficiently carry these chemicals into cancer cells, thus limiting their potential off-target effects. The analysis of the literature showed that HOTAIR, MALAT1, and H19 are the oncogenic lncRNAs most studied in melanoma, while MEG3 is an important tumor suppressor decreased in this cancer. The aberrant expression of these lncRNAs affects several hallmarks of cancer, e.g., proliferation, motility, and epithelial to mesenchymal transition, promoting the melanoma plasticity and drug resistance. In this frame, siRNA, antisense oligonucleotide, and CRISPR-Cas9 genome editing appear to be the most effective nucleic acid strategies to restore the physiologic expression of lncRNA, while curcumin, resveratrol, and quercetin are the main phytochemicals able to target and influence the expression of lncRNAs altered in cancer. Overall, this study provides a comprehensive overview regarding the role of lncRNAs in the phenotype plasticity of melanoma cells and their potential targeting using RNA-based therapy and natural products.

RNA-based interventions are particularly promising for next-generation therapeutic strategies and hold significant potential when integrated with diagnostic modalities. Among noncoding RNAs, microRNAs (miRNAs) regulate gene expression post-transcriptionally and represent compelling targets for cancer therapy. However, their clinical translation remains hindered by instability, off-target effects, and limited delivery efficiency. Here, we report the microfluidic synthesis of hybrid lipid–polymer nanoparticles (LiPoNs) that co-deliver an AntimiR-21 and the magnetic resonance imaging contrast agent gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA). The LiPoNs were obtained using coupled Hydrodynamic Flow Focusing (cHFF), enabling precise control over lipid–polymer self-assembly and surpassing the compositional limitations reported with conventional micromixers. The resulting AntimiR-21–Gd-DTPA–LiPoNs exhibited an average hydrodynamic diameter of 124 nm, narrow polydispersity (PDI < 0.2), and encapsulation efficiency up to 60%. In MDA-MB-231 breast cancer cells, treatment with AntimiR-21–LiPoNs induced suppression of miR-21 and a corresponding decrease in migratory capacity, demonstrating effective functional delivery and gene expression modulation. These findings establish a versatile microfluidic platform for engineering multifunctional lipid–polymer nanostructures whose hybrid architecture combines the biocompatibility and membrane fusion capability of lipids with the structural robustness and controlled release properties of polymers, thereby advancing RNA-based theranostic design for precision oncology and related applications.