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RNA therapy holds great potential for cancer treatment owing to its ability to regulate gene expression precisely, thereby inhibiting tumor growth and metastasis. However, RNA delivery faces several physiological challenges, including rapid degradation by nucleases, limited cellular uptake, and inefficient intracellular release. To address these limitations, stimuli-responsive nanocarriers have been developed to enhance RNA delivery and improve therapeutic efficacy while minimizing side effects. These intelligent systems are designed to respond to specific endogenous or exogenous stimuli (, pH, redox potential, enzyme, light, magnetic fields, and ultrasound), enabling targeted delivery and controlled RNA release. This review highlights recent advances in the design and mechanisms of stimuli-responsive RNA nanocarriers, emphasizing key research findings and exploring future perspectives for their clinical translation.
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http://dx.doi.org/10.7150/thno.112492 | DOI Listing |
Nano Lett
September 2025
State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
An optimal administration approach is critical for effective mRNA delivery and treatment. Nebulizer inhalation offers a mild, convenient, and noninvasive strategy with high translational potential but primarily focused on lung delivery. In this study, we found that surface charges influence tissue targeting of mRNA lipid nanoparticle (mRNA-LNP) postnebulization.
View Article and Find Full Text PDFBrain
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Guangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Rege
Abnormal accumulation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Small interfering RNAs (siRNAs) targeting TDP-43 offer potential therapeutic strategies for these diseases. However, efficient and safe delivery of siRNAs to the central nervous system (CNS) remains a critical challenge.
View Article and Find Full Text PDFBiomaterials
September 2025
State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China.
Retinal neovascularization is one of the most prevalent fundus neovascular diseases, affecting vision and potentially leading to severe complications, such as retinal detachment or irreversible blindness. Current treatments primarily involve intravitreal injections (IVT) of anti-vascular endothelial growth factor (anti-VEGF) agents. However, such treatment often requires repeated injections, develop incomplete responses, and are associated with adverse effects.
View Article and Find Full Text PDFJ Pept Sci
October 2025
Institute of Technology, University of Tartu, Tartu, Estonia.
The development of therapeutic small interfering RNAs (siRNAs) has lately gained significant momentum due to their ability to silence genes in a highly specific manner. The main obstacle withholding the wider translation of siRNA-based drug modalities is their limited half-life and poor bioavailability, especially in extra-hepatic tissues. Consequently, various drug delivery systems (DDSs) have been developed to improve the delivery of siRNAs, including short delivery peptides called cell-penetrating peptides (CPPs).
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
Shanxi Key Laboratory of Nucleic Acid Biopesticides, Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi 030006, China; School of Synthetic Biology, Shanxi University, Taiyuan, Shanxi 030006, China; School of Life Science, Shanxi University, Taiyuan, Shanxi 030006, China.
Glutamine: fructose-6-phosphate aminotransferase (GFAT) is the first rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays a crucial role in various biological processes, including chitin metabolism in insects. Locusta migratoria, a widespread and highly destructive agricultural pest, poses a significant threat due to its rapid reproduction and long-distance migration. In this study, we identified and characterized LmGFAT as a key regulator of locust development.
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