Pattern recognition receptors (PRRs) are crucial immune modulators that orchestrate innate and adaptive immune systems for the regulation of inflammatory responses. Several PRR families and their ligands associated with immune modulation have been identified, which promoted the development of natural and synthetic PRR agonistic ligands as adjuvants in immunotherapy applications. However, conventional adjuvants are mainly based on small molecules, peptides, lipids, and oligonucleotides, which suffer from unfavorable drug-like properties for in vivo applications, including vulnerability to biodegradation, undesirable pharmacokinetic profiles, and poor cellular uptake. Nanoparticle formulation is a promising approach for addressing the issues with conventional adjuvants.

This review aims to provide a broad understanding of nano-adjuvants utilized in cancer immunotherapy. For this purpose, we introduce the background, summarize the current knowledge on PRRs and their ligands for some representative classes, and highlight various nanoparticle platforms that are utilized to construct nano-adjuvants in cancer immunotherapy. We also discuss some design considerations for optimal nano-adjuvant formulations with potent adjuvant activity and desired in vivo performance.

Nanoparticles provide a robust and versatile platform to shape conventional adjuvants into more drug-like formulations, and the preclinical studies and clinical trials have demonstrated their potential in cancer immunotherapy. The emergence of cancer immunotherapy in clinics will fuel continuous efforts toward highly efficient nano-adjuvant systems that can strongly boost the antitumor immune responses in cancer immunotherapy. The accumulated knowledge gained through the progress will provide important insights into optimal nano-adjuvant formulations and potentially guide their clinical translation.