Systemic delivery of the tumor necrosis factor gene to tumors by a novel dual DNA-nanocomplex in a nanoparticle system

Nanocomplexes (NCs) were generated by incubation of the positively charged HCR peptide with the negatively charged pE425-TNF expression vector. To circumvent the instability of pTNF-NCs in plasma, a dual nanocomplex in a nanoparticle system was in turn generated by encapsulation of the pTNF-NCs in polymeric NPs. Intracellular delivery of the pTNF-NC in NPs results in sustained release of the pTNF-NC, import of pE425-TNF to the nucleus and expression of TNF. Our results further support the premise that this system is effective in the delivery of DNA expression vectors to tumors. Intratumoral expression of secreted cytokines, such as TNF, thus represents a novel approach for inducing anti-tumor activity and potentially reprogramming the tumor immune microenvironment.147