Peptide-functionalized nanomaterials for controlled drug delivery and regenerative therapies in retinal diseases

Degenerative retinal diseases, such as diabetic retinopathy, age-related macular degeneration (AMD), and retinitis pigmentosa, cause irreversible vision loss by destroying vital retinal cells and represent major global health concerns. Traditional therapies have limited success in fully restoring vision due to the complex retinal structure and blood-retinal barriers (BRBs), though they may help alleviate symptoms or slow disease progression in some cases. Nanochemistry and peptide-based systems represent breakthrough approaches by leveraging nanoscale precision and biological specificity. This review examines the chemical design and synthesis of nanoparticles (NPs), nanoscaffolds, and peptide conjugates used in retinal neural regeneration. It also explores their biomedical applications, especially in targeted drug delivery, tissue engineering, and cellular repair. Biodegradable polymeric NPs, liposomes, and hybrid nanostructures are designed to cross barriers, release drugs in a controlled manner, and enhance biocompatibility. PEGylation improves stability and reduces immune responses in the ocular environment, while peptide functionalization enables specific cellular targeting and minimizes inflammatory reactions. Peptide-functionalized platforms, such as RGD-modified NPs and self-assembling hydrogels, provide receptor-mediated targeting and extracellular matrix (ECM) mimicry to support retinal regeneration for improved stem cell differentiation and neuroprotection. We discuss drug/gene delivery mechanisms, cellular interactions, and immune modulation, as well as neuroprotection, stem cell therapy, and diagnostic applications. Preclinical studies have demonstrated promising efficacy in animal models; however, concerns regarding scalability, long-term safety, and non-invasive delivery persist. Next-generation technologies, such as stimuli-responsive NPs, computationally designed peptides, and patient-specific delivery systems, are on the horizon to address unmet clinical needs. By marrying nanochemistry's precision with peptides' bioactivity, these technologies have the potential to transform retinal disease treatment, enabling the restoration of vision and an improvement in quality of life for millions of people worldwide.