Challenges of using lipopolysaccharides for cancer immunotherapy and potential delivery-based solutions thereto

Despite being one of the earliest Toll-like receptor (TLR)-based cancer immunotherapeutics discovered and investigated, the full extent of lipopolysaccharide (LPS) potentials within this arena remains hitherto unexploited. In this review, we will debate the challenges that have complicated the improvement of LPS-based immunotherapeutic approaches in cancer therapy. Based on their nature, those will be discussed with a focus on side effect-related, tolerance-related and in vivo model-related challenges. We will then explore how drug delivery strategies can be integrated within this domain to address such challenges in order to improve the therapeutic outcome, and will present a summary of the studies that have been dedicated thereto. This paper may inspire further developments based on reconciling the advantages of drug delivery and LPS-based cancer immunotherapy.