Abstract
To achieve the promise of stimuli-responsive drug delivery systems for the treatment of cancer, they should (1) avoid premature clearance; (2) accumulate in tumors and undergo endocytosis by cancer cells; and (3) exhibit appropriate stimuli-responsive release of the payload. It is challenging to address all of these requirements simultaneously. However, the numerous proof-of-concept studies addressing one or more of these requirements reported every year have dramatically expanded the toolbox available for the design of drug delivery systems. This review highlights recent advances in the targeting and stimuli-responsiveness of drug delivery systems. It begins with a discussion of nanocarrier types and an overview of the factors influencing nanocarrier biodistribution. On-demand release strategies and their application to each type of nanocarrier are reviewed, including both endogenous and exogenous stimuli. Recent developments in stimuli-responsive targeting strategies are also discussed. The remaining challenges and prospective solutions in the field are discussed throughout the review, which is intended to assist researchers in overcoming interdisciplinary knowledge barriers and increase the speed of development. This review presents a nanocarrier-based drug delivery systems toolbox that enables the application of techniques across platforms and inspires researchers with interdisciplinary information to boost the development of multifunctional therapeutic nanoplatforms for cancer therapy.