Disclosed are self-assembling nanoparticle compositions that comprise a plurality of cationic cell penetrating peptides, each covalently linked to a hydrophobic therapeutic molecule (e.g., an antigenic peptide, mRNA, siRNA, DNA, or the like), and optionally, non- covalently bound to at least one TLR (Toll-like receptor) ligand. Also disclosed are methods for use of the nanoparticle compositions in the treatment, prophylaxis, and/or the amelioration of one or more symptoms of a mammalian disease, including, without limitation, cancer, infection, inflammation, and related diseases and abnormal conditions.