Immunotherapy, particularly approaches that combine tumor-specific vaccines with immune checkpoint modulation, represents a promising strategy for overcoming tumor immune evasion. While most mRNA-based cancer vaccines focus solely on antigen delivery, there is a need for platforms that simultaneously enhance antigen presentation and modulate the tumor microenvironment to increase therapeutic efficacy. This study presents a novel dual-nanolipid exosome (NLE) platform that simultaneously delivers MUC1 mRNA and CTLA-4-targeted siRNA in a single system. These endogenous lipid-based nanoparticles are structurally designed to mimic exosomes and are modified with mannose to enable selective targeting to dendritic cells (DCs) via mannose receptors. The platform was evaluated both in vitro and in vivo in terms of mRNA encapsulation efficiency, nanoparticle stability, and uptake by DCs. The co-delivery platform significantly enhanced antitumor immune responses compared to monotherapies. Flow cytometry revealed a notable increase in tumor-infiltrating CD8⁺ T cells (p < 0.01), and ELISPOT assays showed elevated IFN-γ production upon MUC1-specific stimulation. In vivo CTL assays demonstrated enhanced MUC1-specific cytotoxicity. Combined therapy resulted in immune response enhancement compared to vaccine or CTLA-4 siRNA alone. The NLE platform exhibited favorable biodistribution and low systemic toxicity. By combining targeted delivery of dendritic cells, immune checkpoint gene silencing, and efficient antigen expression in a biomimetic nanoparticle system, this study represents a significant advance over current immunotherapy strategies. The NLE platform shows strong potential as a modular and safe approach for RNA-based cancer immunotherapy.

Background/Objectives: Glioblastoma is a highly aggressive brain tumor with limited treatment options and poor prognosis. Signal Transducer and Activator of Transcription 3 (STAT3) plays a crucial role in glioblastoma progression, making it a promising therapeutic target. However, effective delivery of STAT3-silencing agents across the blood–brain barrier remains a significant challenge. This study evaluates the efficacy of Lipid Nanoparticles-EXOSOME COMPLEX STAT3-silencer treatment in reducing glioblastoma tumor growth by facilitating efficient small interfering RNA delivery and inhibiting STAT3 expression. Methods: A novel exosome-based drug delivery system was developed using NLP-EXOSOME COMPLEX nanoparticles loaded with STAT3-silencer siRNA. The therapeutic efficacy was assessed in vitro using human glioblastoma cell lines and in vivo using a glioblastoma mouse model. Tumor progression, STAT3 expression levels, and survival rates were analyzed. Results: The results demonstrated that Lipid Nanoparticles-EXOSOME COMPLEX effectively transported STAT3-silencer siRNA into glioblastoma cells, leading to significant STAT3 downregulation. This resulted in reduced tumor proliferation, increased apoptosis, and extended survival in vivo. The combination of lipid nanoparticles and exosomes provided a stable and efficient delivery mechanism with improved uptake and therapeutic efficacy. Conclusion: Lipid Nanoparticles-EXOSOME COMPLEX STAT3-silencer treatment offers a promising approach for targeted glioblastoma therapy by overcoming the blood–brain barrier limitations and enhancing STAT3 inhibition. Further research is necessary to optimize long-term efficacy, assess potential immune responses, and explore combinatory therapeutic strategies for improved patient outcomes.

Exosomes, a small bilayer membrane derived from eukaryotic cells, have been identified as a useful natural delivery platform due to their suitable size, biocompatibility, structural stability, high loading capacity, and editable surface capability. Due to the difficulty of maintaining the highly pure exosome, several attempts have conducted the techniques for exosome isolation. In recent years, microstructures have found many applications in chemistry, biology, and medicine due to their high accuracy and low cost of materials. Soft lithography is a low-cost, fast, accurate, and yet widely used method of construction of Micron channels. In the present study, a soft lithography process has been performed to construct channels for exosome separation with immunoaffinity function. Both biochemical and biophysical categories tests were performed to examine the quality of extracted exosomes from different sources (serum, cell supernatant, and urine) and compared with the commercially available kit. Results showed that the current technique was capable to isolate exosomes with a high yield rate, purity, and low time consumption. All forms of the imatinib loaded exosomes exhibited the antitumor activity against KYO-1 cell line.

This aimed to validate 21 Oncotype DX gene in a retrospective trial involving women with hormone receptor-positive, human epidermal growth factor receptor type 2 (HER2)–negative, axillary node-negative breast cancer with tumors measuring 1.1 to 5.0 cm in their largest dimension. The ROC curve for each gene, showed the sensitivity of BAG1 and KI67 ranged between 96.08 and 99.46 percent. Survivin and BAG1 had gene specificities ranging from 95.6–100%. The detection threshold ranged from 26.64 to 31.12 copies for MYBL2 and BAC1, respectively; while ranged from 24.25 to 33.83 copies for RPLP0 and ERBB2, respectively. This retrospective research of uniformly treated patients with hormone–receptor–positive, HER2-negative, and axillary node–negative breast cancer demonstrates the clinical validity of the 21-gene assay.

Background/Objectives: Cell-free DNA (cfDNA) is a valuable biomarker for cancer diagnosis and therapy monitoring; however, its low abundance and fragmented nature present major challenges for reliable isolation, particularly from limited plasma volumes. Here, we report the development and evaluation of a novel magnetically assisted microfluidic chip with a three-inlet design for efficient cfDNA extraction from small-volume plasma samples. Methods: The platform enables controlled infusion of plasma, lysis buffer, and magnetic nanoparticle suspensions at defined flow rates. An external magnetic field selectively captures cfDNA-bound nanoparticles while efficiently removing background impurities. Results: Direct comparison with two in vitro diagnostic (IVD)-certified commercial cfDNA extraction kits showed that the microfluidic system achieved comparable cfDNA yields at standard plasma volumes and superior performance at reduced input volumes. High DNA purity and integrity were confirmed by quantitative PCR amplification of a housekeeping gene and clinically relevant targets. The complete workflow required approximately 9 min, used minimal equipment, reduced contamination risk, and enabled rapid processing with future potential for parallel multi-chip configurations. Conclusions: These findings establish the proposed microfluidic platform as a rapid, reproducible, and scalable alternative to conventional cfDNA extraction methods. By significantly improving recovery efficiency from small plasma volumes, the system enhances the clinical feasibility of liquid biopsy applications in cancer diagnostics and precision medicine.