Stimuli-responsive nanogels as promising carriers for controlled drug delivery of anticancer therapeutics

Abstract

Nanogels (NGs), especially those with stimuli responsiveness, have attracted significant attention in the last decades because of their potential for biomedical applications, particularly in the field of cancer therapy research. These nanoparticles are highly promising for therapeutic delivery because of their high biocompatibility with body fluids and tissues as well as their ability to encapsulate high amounts of biologically active agents such as drugs, proteins, and genetic material inside the polymer networks and release the payload in a controlled manner. The designed introduction of specific polymer modalities allows changing ordinary NGs into advanced stimuli-sensitive nanocarriers that undergo physicochemical transitions or chemical changes in their structure (e.g., change their conformation, size and charges, solubility, alter their hydrophilic/hydrophobic balance, or degrade chemical structures) in response to various endogenous and exogenous stimuli. While detecting changes in the tumor microenvironment (pH, enzymes, reactive oxygen species, redox conditions, etc.), NGs can release the payload at the target site without relying on costly systems that require an external source (e.g., magnetic field, light, temperature, etc.) to remotely trigger the release of the payload. The emphasis of this chapter is on the most recent contributions in the arena of endogenous stimuli-responsive NGs, including pH-sensitive, enzyme-sensitive, ROS-sensitive, redox-sensitive NGs, as they can directly detect changes in the internal microenvironment of cancer cells for triggering the release of anticancer therapeutics. Moreover, some dual or multiresponsive NGs that combine different internal and/or external stimuli such as magnetic-responsive, light-responsive, and temperature-responsive NGs are discussed. The biological barriers that need to be overcome for efficient delivery of anticancer therapeutics as well as the relevance of passive and active targeting are described. The fundamental understanding of their responsive behavior against various stimuli with applications in cancer therapy is highlighted, and their future prospective is also discussed.