Peptide-nanoparticle platforms for antisense therapeutics: A coarse-grained modeling approach to brain delivery
Computers in Biology and Medicine, cilt.203, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 203
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.compbiomed.2026.111479
- Dergi Adı: Computers in Biology and Medicine
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, Compendex, EMBASE, INSPEC
- Anahtar Kelimeler: Antisense oligonucleotide, In silico modeling, Nanoparticle delivery, Nasal-to-brain targeting, Neuroinflammation, Peptide conjugation, Traumatic brain injury, TREM2 targeting
- Hacettepe Üniversitesi Adresli: Evet
Özet
Traumatic brain injury (TBI) is a leading cause of long-term neurological deficits, often resulting in complex, unresolved molecular and cellular dysfunctions. Among these, gene–circuit disruptions—particularly those affecting neuroinflammation, oxidative stress, and mitochondrial dynamics—have emerged as critical mediators of post-traumatic neuropathology. In this study, we utilized artificial intelligence (AI)-driven proteomics and RNA sequence integration to map altered signaling pathways following TBI. Computational predictions identified specific gene–circuit nodes susceptible to therapeutic intervention, including redox-sensitive mitochondrial regulators and genes involved in the neuroimmune interface. Importantly, although our analyses are derived from rodent models, the conserved signaling pathways and regulatory circuits identified here provide a translational window with strong relevance to human TBI pathophysiology, thereby bridging preclinical findings with potential therapeutic application. Based on these insights, we designed a suite of responsive nanoparticle formulations optimized in silico for targeted delivery to dysregulated brain regions. These carriers incorporated ligands targeting disrupted circuits and incorporated redox-sensitive release mechanisms. Our platform demonstrates the feasibility of a closed-loop, data-guided strategy that integrates AI-based gene network profiling with rational nanocarrier design. This approach provides a scalable framework for precision neurotherapeutics, particularly for complex disorders such as TBI where conventional monotherapies have proven inadequate.