Nanoparticle mediated targeting of toll-like receptors to treat colorectal cancer

Abstract

Colorectal cancer (CRC) accounts for approximately 10% of all cancer cases worldwide. Conventional treatment has relied on chemotherapy, radiation therapy and surgery with limited success for patients with metastatic CRC. Toll like receptor (TLR) agonists have garnered attention for their ability to stimulate the innate immune system and consequently stimulate production of proinflammatory cytokines and activate an antitumor T cell response. However, activation of TLRs can also result in tumorigenesis and drug resistance depending on the specific TLR and cell that is targeted. Due to these contradictory effects of TLR stimulation, a key challenge is targeting specific cells, such as the dendritic cells or macrophages, to ensure the most optimal result. Additionally, TLR agonists are small molecules that can be cleared rapidly after local administration and can result in severe systemic side effects. This demonstrates the need to develop appropriate nanoparticle delivery systems for TLR agonists that can specifically target the innate immune system as a tool to treat CRC. In this review, the challenges in designing these nanoparticles will be discussed together with the recent advances of nanoparticle formulations containing TLR agonists.

Keywords: Colorectal cancer; Immunotherapy; Nanoparticles; Toll-like receptor agonists; Tumor microenvironment.