To validate the HIV‐inhibition efficacy of MPLN, the human lymphoma (MT2) cell membrane and 12p1 functionalized lipid nanoparticles containing siRNA targeting HIV‐1 tat and rev transcripts were constructed, and their characterization, ability to bind to gp120, HIV‐1 neutralization, ability to deliver siRNA into the cytoplasm of HIV‐1‐infected cells, inhibition of gp120‐induced bystander cell killing, distribution, and safety in vivo were investigated. The gene discussed is ITIH4; the disease is lymphoma.