Receptor agonist/antagonist-incorporated anticancer nanodrugs: Design, materials, and strategies

Abstract

With the continuous discovery of receptors that are closely involved in tumor occurrence and progression, modulating the activity of these receptors to achieve tumor therapy via their agonists/antagonists is regarded as a feasible antitumor strategy. However, conventional agonists/antagonists have their own disadvantages such as low bioavailability and significant off-target effect, which limit the application of agonists/antagonists. Benefiting from the rapidly developing nanotechnology, many studies have tried to integrate agonists/antagonists into nanodrug systems to develop agonist/antagonist-incorporated anticancer nanodrugs, and many of these investigations have achieved satisfactory antitumor effects. In this review, we provide an overview of the agonists/antagonists currently used in nanodrug systems, including pattern recognition receptor agonists, G protein-coupled receptor agonists/antagonists, and nuclear receptor agonists. We provide and discuss the design ideas, carrier materials, preparation methods, and working mechanisms for nanodrug systems based on the aforementioned agonists/antagonists. In some examples, we elaborate on the combinational strategies of agonists/antagonists and other therapeutic reagents. In addition, from different aspects, we also propose the main challenges and future research directions that deserve careful investigations in this field. We hope that this review may provide guidance for the development of agonist/antagonist-incorporated anticancer nanodrugs.