Cell-penetrating peptides as a gateway for nanocarrier-mediated glioblastoma therapy

The most virulent primary brain cancer is Glioblastoma Multiforme (GBM), which is defined mainly by poor survival and drug delivery failure as a therapy. The blood-brain barrier (BBB) restricts the passage of nearly all macromolecular drugs. The presence of a heterogeneous blood-tumor barrier (BTB) at invasive fronts is primarily accountable for recurrence location. This review helps in understanding the key role of CPP-functionalized Nanocarriers (NCs) in effective brain tumor targeting and crossing biological barriers. Conjugation of CPPs with NCs facilitates receptor-mediated transcytosis across the BBB and allows efficient endosomal release and targeted intracellular delivery within GBM cells and drug-resistant Glioma Stem Cells (GSCs). In addition, the review evaluates the hybrid platforms including CPP-liposomes, polymeric NCs, Dendrimers, and Inorganic NCs that utilize dual targeting and stimulus-responsive activation approaches for targeted delivery and synergy. Increased brain uptake and drug delivery by using the CPPs conjugated NCs are being viewed in preclinical studies. The novel synergy of peptide engineering and nanotechnology holds a distinctive potential to overcome both therapeutic resistance and delivery constraint, enabling efficient, personalized GBM nanomedicine.