Self-assembled Nanogel Engineering for Advanced Biomedical Technology

Abstract

Nanogels are polymer nanoparticles with three-dimensional networks. Recently, various nanogels have been designed, with a particular focus on biomedical applications. In this review, we describe recent progress in the synthesis of functional nanogels by self-assembly of associating polymers and nanogel engineering for advanced biomedical technology including regenerative medicine and drug delivery systems. Ç IntroductionLiving systems, for example biomembranes which are selforganized assemblies of proteins and lipids, reveal sophisticated biological functions such as signal transduction, energy production, and cellular communication. The concept of supramolecular assembly of biocomponents such as lipids, proteins, nucleic acids, and polysaccharides is central to bottom-up design of advanced biomaterials. For example, molecular organization based on supramolecular assembly enables fabrication of not only materials with well-controllable molecular orientation and arrangement but mechanically controlled nanomaterials and nanosystems 1 or self-assembled micro-and nanoshells for drug delivery applications. Recently, we have proposed nanogel engineering, which involves design of self-assembled nanogel and the construction of functional hierarchical gels or interfaces through their bottomup assembly of nanogels as building units. The bottom-up nanogel engineering provides a new paradigm for development of hydrogel biomaterials with well-organized three-dimensional structures, multiple functions, sensitivity to a range of different stimuli, and programmed responses that can be controlled temporally and spatially. Nanogels are nanometer-sized hydrogel nanoparticles (<100 nm) with three-dimensional networks of crosslinked polymer chains. They have attracted growing interest over the last several years due to their potential for biomedical applications, such as drug delivery system (DDS) and bioimaging.3 Usual polymer nanoparticles, such as nanospheres, have a densely packed polymer inside core structure. In contrast, nanogels are able to stably trap bioactive compounds such as drugs, proteins, and DNA/RNA inside their nanospace with polymer networks. Moreover, nanogels show a rapid response to microenvironmental factors such as temperature and pH because of their nanoscale dimensions. These properties are useful for the controlled release of bioactive compounds.Nanogels have been prepared using various methods, which can be classified into two categories according to their crosslinking structure: chemically (covalent) crosslinked nanogels which form crosslinking points by covalent bonds and physically crosslinked nanogels with noncovalent bonds (such as hydrogen bonds), electrostatic and hydrophobic interactions. 4 Typically, chemically crosslinked nanogels are synthesized under dilute conditions by a crosslinking reaction of polymers modified with reactive groups, such as vinyl and thiol groups. Nano-or microemulsion polymerization methods are often used to obtain nanogels with a well-controlled size.A variety of...

A Hybrid Hydrogel Biomaterial by Nanogel Engineering: Bottom‐Up Design with Nanogel and Liposome Building Blocks to Develop a Multidrug Delivery System

“…Nanogels are attracting growing interest as nanocarriers in drug delivery systems. [27][28][29] In general, nanogels can be classifi ed as either chemically or physically crosslinked nanogels. Chemically crosslinked nanogels are formed by crosslinking of the constituent polymers by covalent bonds.…”

“…[ 31 ] The closed association of polymers at the nanosize scale is governed by many factors, including the concentration of the associating polymers, the structure and concentration of the crosslinking points, and the characteristics of the associating polymers. [ 29 ] Generally, conventional self-assembled amphiphilic nanoparticles, such as polysoaps (20-100 mol% hydrophobic group content) and proteins (ca. 50 mol% hydrophobic amino acid content), contain a large number of hydrophobic groups within the polymer chains.…”

The Taming of the Maleimide: Fabrication of Maleimide‐Containing ‘Clickable’ Polymeric Materials

“…Apart from macroscopic hydrogels, recent years have witnessed an increase in utilization of nanogels for biomedical applications. Due to their nanometric size, water dispersibility, and their ability to carry payloads such imaging agents or drugs to diseased cells through passive or active targeting, they are attractive platforms for diagnostics and drug delivery ,. Recently, we devised a strategy to fabricate maleimide functional group containing nanogels that allow facile functionalization of thiol‐containing molecules (Figure a) .…”

Bio-inspired synthesis of polymer–inorganic nanocomposite materials in mild aqueous systems

“…25 Biomedical applications of CHP nanogels have been investigated, especially applications involving their use as drug delivery system carriers of proteins, drugs and semiconductor nanocrystals. 35 However, CHP nanogels are not very stable, especially in the bloodstream, because of their physical crosslinking structure. It is expected that a hybrid composite formed from calcium phosphate and nanogel may exhibit improved stability and controlled-release properties.…”