Nanomaterials as Smart Immunomodulator Delivery System for Enhanced Cancer Therapy

Immunomodulatory therapeutics, which is conducive to overcoming tumor tolerance and restoring normal immune responses, has been proposed as a promising approach for enhanced cancer therapy and clinical advancement. However, issues including cytokine syndrome, inefficient delivery, hepatic dysfunction, and severe adverse reactions remain to be resolved. It is particularly critical to develop delivery technologies to overcome these limitations and further improve antitumor efficacy. With the continuous development of materials science, biomaterials have been widely used in the field of cancer treatment and have also provided exciting solutions to overcome the bottleneck of immunomodulatory therapeutics. A range of biomaterials, especially nanomaterials, has been developed as a local immunomodulatory platform to enhance targeted delivery, maintain drug stability, and reduce toxicity and side effects. In addition to single immunomodulatory therapeutics, nanomaterials have been demonstrated to possess significant potential in immunomodulatory therapeutics-based synergistic therapies, especially in combination with phototherapy, radiotherapy, chemotherapy, and immune checkpoint blockade. In this review, as background to the discussion of immunomodulatory therapeutics, we first described the mechanisms of action of multiple immunomodulators and discussed their current targeting agents. On this basis, we highlighted the latest advances in the use of nanomaterials-assisted immunomodulatory therapeutics and combination therapy to enhance anticancer immunity. In addition, current challenges and further promises for immunomodulatory therapeutics were also presented.