The treatment of antibiotic-resistant bacterial infections is an unmet therapeutic need, due to the rapid emergence of resistant strains and the low level of investment in new therapeutics. The use of nanoparticles to enhance activity of current therapeutics, and to enable new approaches based on nucleic acid therapeutics, will be described.  Our effort focuses on the use of porous silicon nanoparticles, and systems that deliver small molecule antibiotics or siRNA against inflammatory macrophages will be used as examples.  Attachment of functional peptides imparts specific targeting and cell penetration properties to the constructs that show improved gene silencing and therapeutic outcomes in vivo.