pH-dependent release of CO2 from encapsulated metformin co-delivered with an siRNA for silencing FGL1 expression—the ligand for lymphocyte-activation gene 3 (LAG3), a known immune checkpoint receptor—reduced the immunosuppressive nature of the tumor microenvironment and improved the tumor-free survival in a mouse model for triple negative breast cancer significantly [196]. The gene discussed is LAG3; the disease is neoplasm.