When loaded with siRNA against heme oxygenase-1 (HO1), a chemoresistance-related molecule in tumor cells and an immunotherapeutic molecule in tumor myeloid cells, anti-PD-L1-LNPs were able to induce HO1-inhibition in tumor cells to sensitize chemotherapeutics and reprogram tumor myeloid cells to drive the “cold-to-hot” transition, resulting in an improved response to anti-PD1 antibody therapy in a triple combination study. Here, CD274 is linked to neoplasm.