Innovative nanoparticle-based therapies for pancreatic neuroendocrine tumours (PNETs): advances, challenges, and future directions

Pancreatic neuroendocrine tumours (pNETs), especially in metastatic or unresectable stages, pose major therapeutic challenges. Conventional treatments often show limited effectiveness, creating the need for novel strategies. Nanoparticle-based therapies have emerged as a promising approach. These therapies enable precise drug delivery using the enhanced permeability and retention (EPR) effect, which allows for targeted tumour treatment and reduced systemic toxicity. Nanoparticle-based therapies can encapsulate a variety of therapeutic agents, including cytotoxic drugs and molecular inhibitors, offering the potential for personalised treatment strategies. Recent pharmacological advancements, such as the multi-kinase inhibitors sorafenib, lenvatinib, and axitinib, target key tumour growth and angiogenesis pathways, improving treatment outcomes. In addition, peptide receptor radionuclide therapy (PRRT) and targeted therapies, including tyrosine kinase inhibitors (TKIs), provide alternative approaches that enhance efficacy while reducing adverse effects. The integration of nanoparticle-based delivery systems, including gold, silver, and lipid nanoparticles, enhances drug targeting and controlled release. However, the clinical translation of these technologies remains hindered by factors such as tumour heterogeneity, drug resistance, and challenges related to manufacturing, stability, and regulatory approval. Despite these barriers, advances in “smart” nanoparticles and personalised nanomedicine continue to drive progress, optimising therapeutic precision and minimising toxicity. While challenges persist, nanoparticle-based therapies offer considerable potential for improving pNET treatment. Ongoing research and multidisciplinary collaboration are crucial to overcoming existing limitations, facilitating clinical translation, and ultimately enhancing patient outcomes.