The Next Wave of Immunotherapy: A Critical Review of Nanotechnology Strategies for Immune Checkpoint Blockade

The occurrence of cancer is continuing to rise globally and it has been estimated that cancer-related deaths can reach up to 16.3 million by 2040. The immune system has significant contribution in the fight against tumors; nonetheless, the capacity of tumors to escape the strong response induced by the immune system makes cancer a hard-to-treat disease. In recent times, cancer immunotherapy (IMT), particularly immune checkpoint inhibitors (ICPIs), has emerged as an innovative therapeutic approach in the oncology field; however, ICPIs suffer from several drawbacks that limit their therapeutic effectiveness. Therefore, it is crucial to develop a drug delivery system that can increase the therapeutic efficacy of ICPIs and decrease the side effects associated with their use. In order to develop a safe and effective cancer IMT, modifications of nano-biomaterials and development of nanocarrier (NC)-based drug delivery systems can overcome several challenges by improving bioavailability, delivering ICPIs toward targeted areas, enhancing the antitumor immunity, and achieving tumor microenvironment remodeling. NCs also have the potential to exert synergistic effects along with ICPIs. NCs can play a dual role by acting as a targeted delivery system and by combining therapies. The combination of NCs and ICPIs also has the potential to synergize with chemotherapy, radiation, embolization, and tumor ablation to optimize therapeutic outcomes and reduce treatment-associated toxicity. Therefore, this review has focused on revealing the potential of nanotechnology in the field of ICP blockade. In this review, various aspects including NC-mediated targeted delivery of ICPIs and applications of NCs as part of the combination IMT involving ICPIs have been extensively discussed based on numerous potential study findings.