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

Abstract

Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving DNA expression vectors encoding inflammatory cytokines in tumor cells. The DNP system consists of a DNA expression vector-cationic nanocomplex (NC) surrounded by a diblock polymeric NP. Tumor necrosis factor alpha (TNF) was selected as the prototype cytokine for this system, based on its pleotropic inflammatory and anti-cancer activities. Our results demonstrate that the DNP system is highly effective in driving expression of TNF in tumor cells. We also demonstrate that the DNPs are effective in inducing apoptosis and anti-tumor activity. These findings support a novel immunotherapeutic approach for the intratumoral delivery of DNA vectors that express inflammatory cytokines.

Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma

“…New perspectives concerning intervention seem possible, and the use of nanotechnology could be a powerful approach to the use of cytokines in the prevention and treatment of cancer [ 302 – 304 ]. A better understanding of the relationship between inflammation and myeloma will ensure more effective therapeutic interventions.…”

Poly(Ethylene Glycol)–Polylactide Micelles for Cancer Therapy

“…The DNP system was consisted of a DNA expression vector–cationic peptide nanocomplex (NC) surrounded by a PEG–PLA nanoparticle. The results showed that the DNP system could effectively induce apoptosis of tumor cells and possess highly anti-tumor efficacy in vivo (Shukla et al, 2017 ).…”

Polymeric nucleic acid delivery for immunoengineering

“…Transfecting tumor cells to express these cytokines would be another way to achieve this effect locally [44–46]. For example, a cationic polypeptide was used in one study to form nanocomplexes with plasmid DNA encoding tumor necrosis factor alpha (TNF-α) [47]. These nanocomplexes could be delivered either intratumorally or systemically and led to dramatically slower tumor growth in a breast tumor model.…”