Nanoengineered immune check point inhibitors delivery for targeted brain cancer treatment: Current status and future perspectives

Brain tumors create special difficulties because of their position and the protective covering of blood brain barrier (BBB) that restricts efficient medication access. Treatment alternatives such as surgery and chemotherapy demonstrate poor performance against severe brain tumors. The use of immune checkpoint inhibitors (ICIs) hints at effective cancer therapy; however, their application to brain cancer faces challenges due to inefficient delivery through the BBB and the tumor's suppressive environment. Nanoengineering can increase the transport of ICIs to brain tumors. Numerous nano-delivery systems such as liposomes and micelles have explored ways to avoid the BBB via transcytosis and the EPR mechanism. Functionalization of nanocarriers enhances targeting tumor cells and improves treatment accuracy. New developments involve delivering ICIs together with adjuvants to change the TME and focusing on immune cells such as TAMs and Tregs to boost immunity against tumors. Nanoengineered ICIs have shown effective improvement in animal models by reducing toxicity and enhancing efficacy. Converting these successes into real clinical trials is not easy as they face regulatory concerns and safety challenges. Clinical trials currently examine the use of nanocarriers for treating brain cancer; however, scalability’ and ’long-term safety’ continue to pose challenges. Future approaches will focus on combining customized medicine with advanced nanotechnology and AI to refine treatment methods. Despite obstacles ahead, nanotechnology-based ICIs offer a hopeful approach to enhance brain cancer efficacy and address existing therapeutic constraints. © 2025 Elsevier Inc.