Such SPNDNH were designed to contain three key reshapers to remodel the complex tumor microenvironment of orthotopic pancreatic cancer: i) HAase degraded hyaluronic acid in tumor ECM stroma, ii) H2S donor released H2S to alleviate the tumor hypoxia via inhibiting cell respiration and oxygen consumption, and iii) NLG919 blocked IDO activity to reverse the immunosuppressive tumor microenvironment. The gene discussed is IDO1; the disease is pancreatic neoplasm.