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In this study, we determined effects of an anionic siRNA delivery vector, siRNA ternary complex, which is constructed with biodegradable dendrigraft poly-L-lysine (DGL) and γ-polyglutamic acid (γ-PGA) on the melanoma cells and melanoma lung metastasis. The siRNA ternary complex showed high cellular uptake and silencing effect in melanoma cell line B16-F10/Luc cells. After intravenous administration of the siRNA ternary complex, high silencing effect was also observed in the lung of B16-F10/Luc melanoma metastasis model mice. Therefore, we applied vascular endothelial growth factor (VEGF)-siRNA on the siRNA ternary complex and determined the effect on the melanoma lung metastasis. The siRNA ternary complex containing VEGF-siRNA reduced VEGF protein levels significantly in and , and the complex successfully inhibited melanoma lung metastasis. This biodegradable and effective siRNA delivery vector, siRNA ternary complex, could be available for clinical trials.
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http://dx.doi.org/10.1080/1061186X.2024.2362361 | DOI Listing |
J Virol
April 2025
Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, Florida, USA.
RNA interference (RNAi) is a posttranscriptional gene silencing mechanism acting as an antiviral defense in eukaryotes. During viral replication, intermediate double-stranded RNAs are processed into virus-derived small interfering RNAs (vsiRNAs) by the host enzyme, DICER. These vsiRNAs are incorporated into the RNA-induced silencing complex (RISC), where AGO2 cleaves viral genomic RNAs.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
CONRAD, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
This manuscript provides a comprehensive review of advancements in dry powder inhaler (DPI) technology for pulmonary and systemic drug delivery, focusing on proteins, peptides, nucleic acids, and small molecules. Innovations in spray-drying (SD), spray freeze-drying (SFD), and nanocarrier engineering have led to enhanced stability, bioactivity, and aerosol performance. Studies reveal the critical role of excipients, particle morphology, and device design in optimizing deposition and therapeutic efficacy.
View Article and Find Full Text PDFEur J Pharm Sci
March 2025
Massachusetts College of Pharmacy and Health Sciences (MCPHS University) Department of Pharmaceutical Sciences, School of Pharmacy, 19 Foster St., Worcester, MA 01608, USA. Electronic address:
Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions.
View Article and Find Full Text PDFACS Appl Mater Interfaces
October 2024
Department of Respiratory Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, People's Republic of China.
Cisplatin resistance significantly impacts the antitumor efficacy of cisplatin chemotherapy and contributes to poor prognosis, including metastasis. In this study, we present the utilization of metal-organic framework (MOF) nanoparticles as the therapeutic component and drug loading scaffold for implementing a ternary combination therapeutic strategy to combat cisplatin-resistant lung cancer and metastasis. Specifically, by engineering MOFs (Cis@MOF-siVEGF) through the self-assembly of THPP as photosensitizer for photodynamic therapy (PDT), along with the incorporation of cisplatin (DDP) and VEGF siRNA (siVEGF), we propose the leverage of photodynamic-induced oxidative damage and gene silencing of the angiogenic factor to reverse cisplatin resistance and sensitize therapeutic potency.
View Article and Find Full Text PDFJ Drug Target
August 2024
Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.