Nucleic acid-based therapies have the potential to address numerous diseases that pose significant challenges to more traditional methods. RNA-based therapies have emerged as a promising avenue, utilizing nanoformulation treatments to target a range of pathologies. Nanoformulation offers several advantages compared to other treatment modalities, including targeted delivery, low toxicity, and bioactivity suitable for drug loading. At present, various types of nanoformulations are available, such as liposomes, polymeric nanoparticles (NPs), magnetic NPs, nanoshells, and solid lipid nanoparticles (SLNs). RNA-based therapy utilizes intracellular gene nanoparticles with messenger RNA (mRNA) emerging prominently in cancer therapy and immunotechnology against infectious diseases. The approval of mRNA-based technology opens doors for future technological advancements, particularly self-amplifying replicon RNA (repRNA). RepRNA is a novel platform in gene therapy, comprising viral RNA with a unique molecular property that enables the amplification of all encoded genetic information countless times. As a result, repRNA-based therapies have achieved significant levels of gene expression. In this context, the primary objective of this study is to furnish a comprehensive review of repRNA and its applications in nanoformulation treatments, with a specific focus on encapsulated nanoparticles. The overarching goal is to provide an extensive overview of the use of repRNA in conjunction with nanoformulations across a range of treatments and therapies.

Among the most malignant cancers, oral squamous cell carcinoma (OSCC) stands out as the most common malignant head and neck tumor. Despite advances in the field of treatment, the prognosis of patients with OSCC remains poor. Aiming to overcome the limitations of the currently existing therapies against OSCC, the present work aims to investigate the potential of photodynamic therapy (PDT) with phenothiazine derivatives used alone or in combination. The incorporation of methylene blue (MB) and toluidine blue (TB) was evaluated in OSCC cell lines (HSC-3 and SCC-9) and a nontumor cell line (Hfib). Both compounds exhibited concentration and time-dependent incorporation, with higher rates observed in tumor cells. Regarding dark-phase cytotoxic activity, SCC-9 cells were the most sensitive cell line with an IC₅₀ value of 362.6 µM and 41.4 µM for MB and TB, respectively. Using PDT, all lineages showed greater sensitivity, presenting lower IC₅₀ values when compared to the dark phase values. The combination index values of 0.69 (dark phase) and 0.73 (clear phase) associated with concave isobolograms, in both phases, revealed that MB and TB have synergistic effects when combined against SCC-9 cells. These findings suggest that MB or TB assisted with PDT holds promise for OSCC treatment.

Inflammation plays a central role in various pathological conditions, necessitating the search for safer and more effective anti-inflammatory agents. This study investigates the anti-inflammatory activity of caulerpin, a bisindolic alkaloid isolated from Caulerpa racemosa. In vitro assays demonstrated that caulerpin significantly reduced nitric oxide, TNF-α, IL-6, and IL-12 levels in macrophages stimulated with LPS + IFN-γ, without affecting cell viability. In silico toxicity predictions using Protox 3.0 reinforce a favorable safety profile of caulerpin. Molecular docking and molecular dynamics simulations revealed its high-affinity binding to the glucocorticoid receptor ligand-binding domain (GR-LBD), suggesting a mechanism of action similar to dexamethasone. The involvement of the glucocorticoid receptor was confirmed by the partial reversal of caulerpin’s effects upon RU486 treatment. In vivo, caulerpin exhibited a favorable safety profile, with no signs of acute toxicity at an oral dose of 100 mg/kg. Moreover, in a mouse model of endotoxic shock, caulerpin administration significantly improved survival rates in a dose-dependent manner, providing complete protection at 4 mg/kg. These findings highlight caulerpin as a promising candidate for the development of novel anti-inflammatory therapies. Further studies are warranted to explore its pharmacokinetics, optimize its structure, and evaluate its efficacy in chronic inflammatory diseases.