Nanogels: A chemically versatile drug delivery platform

Nanogels are crosslinked polymeric nanoparticles that exhibit characteristics of an ideal vehicle for therapeutics delivery. These nanocarriers are highly tunable due to the ability of using a variety of chemistries and building blocks in their design, facilitating tailoring of their overall size, surface charge, and payload release behavior. Furthermore, nanogels are compatible with a range of payloads such as small molecules and macromolecules. The level of control over drug loading and drug release parameters achievable via nanogels is superior to common nanocarriers due to this platform's chemical flexibility, which is amenable to bottom-up and fully covalent synthetic approaches. The modular nature of the nanogel platform facilitates many variations in nanoparticle design, resulting in nanomaterials with complex morphologies, hybrid physicochemical properties and responsiveness to environmental stimuli. "Smart" nanogels are capable of triggered release of the encapsulated payload in response to pH modifications, presence of enzymes, temperature fluctuations, and changes in the concentration of reductants and oxidizers in the surrounding milieu, in addition to physical triggers such as heat and light. The bioconjugation of nanogels with targeting elements yields highly selective multifunctional entities with potential for precision drug delivery applications. This review aims at providing a comprehensive summary of chemical synthesis methods for nanogel development for drug delivery applications. Aspects regarding targeting, encapsulation mechanisms and the reactivity of stimuli-responsive nanogels are covered with the intent of giving the reader an insight in the fundamental chemical principles influencing the rational design of nanogels for drug delivery.