Intelligenza artificiale e nanomedicine teranostiche funzionalizzate con peptidi targettanti per il trattamento selettivo del glioblastoma

Nanomedicine has revolutionized oncology by leveraging nanoscale materials to enhance drug delivery, optimize pharmacokinetics, and minimize systemic toxicity. A key advantage of this technology is the ability to functionalize nanoparticles with targeting moieties, such as peptides, antibodies, or small molecules, enabling selective drug accumulation in pathological tissues. This targeted strategy not only improves therapeutic efficacy but also minimizes off-target effects, thereby improving the safety profile of anticancer treatments. Several nanomedicine formulations have already reached the clinic, including liposomal doxorubicin (Doxil®), albumin-bound paclitaxel (Abraxane®), and liposomal irinotecan (Onivyde®), demonstrating the translational potential of this approach. One of the most challenging applications of nanomedicine is the treatment of Glioblastoma Multiforme (GBM), the most aggressive and lethal primary brain tumor in adults. Despite the current standard of care, maximal surgical resection followed by radiotherapy and temozolomide (TMZ)-based chemotherapy, GBM remains highly resistant to conventional treatments and frequently recurs. Its treatment is particularly difficult due to multiple factors, including pronounced tumor heterogeneity, diffuse infiltration into surrounding brain tissue, and the presence of the blood-brain barrier (BBB), which severely limits drug delivery to the tumor site. The five-year survival rate remains below 5%, highlighting the urgent need for more effective therapeutic strategies. Nanoparticles have shown great potential in overcoming these challenges by improving drug solubility and stability, facilitating translocation across the BBB, and enhancing tumor penetration. In particular, the conjugation of nanoparticles with tumor-homing peptides represents a promising approach for selective nanomedicine. Compared to other targeting moieties, such as antibodies or aptamers, peptides offer distinct advantages, including enhanced cell penetration capability, high specificity, low immunogenicity, and cost-effective production. Among these, C-end Rule (CendR) peptides have attracted significant interest due to their specific affinity for neuropilin-1 (NRP-1) receptors, enabling deep tumor penetration. This property is particularly advantageous for GBM therapy, as it enhances drug distribution within the tumor microenvironment. Recent in vitro and in vivo studies have demonstrated that CendR-functionalized nanoparticles improve therapeutic efficacy by increasing drug accumulation in GBM cells and overcoming key limitations of conventional therapies. In this study, we developed a Hybrid lipid-polymer nanosystem functionalized with a CendR tumor-homing peptide for the selective treatment of GBM. By integrating cutting-edge nanotechnology with molecular targeting strategies, our approach aims enhance tumor penetration and reduce systemic toxicity. Our investigation contributes to the development of innovative GBM therapies and provides insights for future nanomedicine applications in oncology.