Cell-penetrating proteins and peptides as a promising theragnostic agent for neurodegenerative disorder

Cell-penetrating peptides (CPPs) have emerged as sophisticated drug delivery mechanisms capable of transporting therapeutic cargo, such as proteins, peptides, nucleic acids, and nanocarriers, into cells. Despite extensive clinical trials, the CPP-based drugs are yet to arrive to the market. This review paper explores the molecular mechanisms underlying the cellular uptake of CPPs and their potential applications in treating neurodegenerative diseases by facilitating the transport of large molecules across the blood-brain barrier (BBB). The study highlights the challenges associated with delivering larger, hydrophilic drugs across the BBB, emphasizing the need for optimizing CPPs for efficient cellular transport and organelle targeting. The selective permeability feature of BBB presents a formidable challenge for developing effective treatments against neurological conditions. Moreover, the significance of targeting specific cellular organelles, including mitochondria, Golgi apparatus, and endoplasmic reticulum, is discussed in relation to various neurodegenerative conditions. These investigations have demonstrated that CPP can enhance drug delivery across the BBB, improving therapeutic outcomes. Furthermore, the integration of nanomaterials with CPPs represents a potent strategy to augment drug delivery capabilities for central nervous system disorders. This combination not only enhances the bioavailability of therapeutic agents but also enables targeted delivery to specific cellular sites within the brain. The applications of CPPs go beyond drug delivery to include diagnostic imaging and theragnostic strategies for various diseases. The study concludes that CPPs offer a groundbreaking potential for addressing neurodegenerative disorders, additional research and clinical trials are essential to overcome the current challenges and enhance their therapeutic applications.