Research

Nano-Immuno-Oncology

Nano Immuno Oncology

Nano-immuno-oncology is an emerging cross field that harnesses nanotechnology’s unique synergy with immunology to advance cancer immunotherapy. Human immune system has evolved to sense and respond to nano- and micro-particulates (e.g., viruses, bacteria). Through the versatile control of composition, size, shape, and surface properties of nanoparticles, nano-immune-engineering approaches are uniquely positioned to mount appropriate immune responses against cancer. Our lab is leveraging the all-or-nothing protonation cooperativity of the ultra-pH sensitive nanoparticles to augment the cancer-immunity cycle toward anti-tumor immunity. These efforts include T cell activation in lymph nodes by coordinating cytosolic delivery of tumor antigens to dendritic cells with simultaneous activation of stimulator of interferon genes (STING), or tumor-targeted delivery of acidotic inhibitors to overcome T cell retardation.  Recently, we discovered PC7A polymer as a polyvalent STING agonist that stimulates prolonged production of proinflammatory cytokines with improved dendritic cell-T cell priming over natural STING ligand. Through an NCI-sponsored U54 Nano-Immune-Engineering Center Award, we are integrating molecular immunology, biomedical engineering and clinical oncology to advance cancer immunotherapy.

Selected publications:

  • Wang Z, Luo M, Mao C, Wei Q, Zhao T, Li Y, Huang G, Gao J. A Redox-Activatable Fluorescent Sensor for the High-Throughput Quantification of Cytosolic Delivery of Macromolecules. Angew. Chem. Int. Ed. 2016, 55, 1-6. PDF
  • Luo M, Wang H, Wang Z, Cai H, Lu Z, Li Y, Du M, Huang G, Wang C, Chen X, Porembka MR, Lea J, Frankel AE, Fu Y, Chen ZJ, Gao J. A STING-activating nanovaccine for cancer immunotherapy, Nature Nanotech. 2017, 52. PDF
  • Luo M, Liu Z, Zhang X, Han C, Samandi L, Dong C, Sumer BD, Lea J, Fu Y, Gao J. Synergistic STING activation by PC7A nanovaccine and ionizing radiation improves cancer immunotherapy. J. Controlled Release. 2019, 300, 154-160. PDF
  • Li S, Bennett ZT, Sumer BD, Gao J. Nano-Immune-Engineering Approaches to Advance Cancer Immunotherapy: Lessons from Ultra-pH-Sensitive Nanoparticles. Acc. Chem. Res. 2020, 53, 11, 2546-2557. PDF
  • Li S, Luo M, Wang Z, Feng Q, Wilhelm J, Wang X, Li W, Wang J, Choka A, Fu Y, Sumer BD, Yu H, Gao J. Prolonged activation of innate immune pathways by a polyvalent STING agonist. Nature Biomed. Eng. 2021, 5, 455-466. PDF