Owing to the unique advantages of combining the characteristics of hydrogels and nanoparticles, nanogels are actively investigated as a promising platform for advanced biomedical applications. In this work, a self‐cross‐linked hyperbranched polyglycerol nanogel is synthesized using the thiol–disulfide exchange reaction based on a novel disulfide‐containing polymer. A series of structural analyses confirm the tunable size and cross‐linking density depending on the type of polymer (homo‐ or copolymer) and the amount of reducing agent, dithiothreitol, used in the preparation of the nanogels. The nanogels retain not only small molecular therapeutics irrespective of hydrophilic and hydrophobic nature but also large enzymes such as β‐galactosidase by exploiting the self‐cross‐linking chemistry. Their superior biocompatibility together with the controllable release of active therapeutic agents suggests the applicability of nanogels in smart drug delivery systems. 相似文献
Cancer‐cell‐specific pH‐activatable polymer nanogels consisting of CD44‐receptor‐targeting hyaluronic acid (HA), pH‐sensitive poly(β‐amino ester) (PBAE), and near‐infrared (NIR) fluorescent indocyanine green (ICG) were synthesized and used to detect cancer cells. The HA/PBAE/ICG‐polymer‐nanogel‐based NIR probe was nonfluorescent outside of tumor cells. After internalization by CD44‐receptor‐mediated endocytosis, the probe accumulated in the late endosomes or lysosomes where the acidic pH solubilized the PBAE and caused instant disassembly of the polymer nanogel. During endosomal maturation, the encapsulated ICG was released from its quenched state, inducing strong NIR fluorescence recovery. The nanogels generate a highly tumor‐specific NIR signal with a reduced background signal. 相似文献
Nanogels are swollen nanosized networks composed of hydrophilic or amphiphilic polymer chains. They are developed as carriers for the transport of drugs, and can be designed to spontaneously incorporate biologically active molecules through formation of salt bonds, hydrogen bonds, or hydrophobic interactions. Polyelectrolyte nanogels can readily incorporate oppositely charged low‐molecular‐mass drugs and biomacromolecules such as oligo‐ and polynucleotides (siRNA, DNA) as well as proteins. The guest molecules interact electrostatically with the ionic polymer chains of the gel and become bound within the finite nanogel. Multiple chemical functionalities can be employed in the nanogels to introduce imaging labels and to allow targeted drug delivery. The latter can be achieved, for example, with degradable or cleavable cross‐links. Recent studies suggest that nanogels have a very promising future in biomedical applications. 相似文献
In this study, we report pH‐responsive polysaccharidic nanogels comprising starch grafted with 3‐(diethylamino)propylamine (DEAP, as an inner soft nanogel core) and poly(ethylene glycol) (PEG, as an outer hydrophilic nanogel shell). Here, the DEAP moieties (pKb ~ pH 7.0) enhance the lipophilicity of the nanogel core at pH 7.4, improving the loading efficiency of an antitumor model drug (docetaxel [DTX]) in the core. However, the DEAP moieties could be protonated below pH 7.0, resulting in the mediation of ion‐dipole interactions with hydroxyl groups abundant in starch backbone. This event causes the electrostatic condensation of the nanogel core and enables the acceleration of drug release by squeezing of the core. We demonstrated that the nanogels selectively release the drug given a weakly acidic pH stimulus. These drug release trends are reversible with changes in pH. As a result, the nanogels are able to efficiently reduce MDA‐MB‐231 tumor cell population in acidic pH environments. 相似文献
Rapidly shrinking poly(N‐isopropyl acrylamide) (PNIPAM) hydrogels are prepared by crosslinking with self‐assembled nanogels that consist of cholesteryl‐ and methacryloyl‐substituted pullulan (CHPMA). The CHPMA nanogel (Rh = 26.4 nm) was used as a crosslinker for a hydrophilic nanodomain. Transmission electron microscopy images of the nanogel‐crosslinked PNIPAM hydrogel reveal a well‐defined nanoporous structure. The nanogel‐crosslinked PNIPAM hydrogel shows rapid shrinking based on its structure. The shrinking half‐time was ≈2 min, which is about 3 400 times faster than that of a PNIPAM hydrogel crosslinked by methylene(bisacrylamide).
Thermoresponsive polymers change their physical properties as the temperature is changed and have found extensive use in a number of fields, especially in tissue engineering and in the development of drug delivery systems. The synthesis of a novel core–shell nanogel composed of N‐isopropylacrylamide and sulfobetaine by reversible addition fragmentation chain transfer polymerization is reported. The core–shell architecture of the nanogels is confirmed using energy dispersive X‐ray spectroscopy in scanning transmission electron microscopy. These nanogels exhibit dual thermoresponsive behavior, i.e., the core of the nanogel exhibits lower critical solution temperature, while the shell displays upper critical solution temperature behavior. Transition temperatures can be easily tuned by changing the molecular weight of the constituent polymer. These nanogels can be efficiently used in temperature‐triggered delivery of therapeutic proteins and drugs. 相似文献
Selective activation of photocatalysts under constant light conditions has recently been targeted to produce multi‐responsive systems. However, controlled activation, with easy recovery of the photocatalysts, induced by external stimuli remains a major challenge. Mimicking the responsiveness of biological systems to multiple triggers can offer a promising solution. Herein, we report dual‐responsive polymer photocatalysts in the form of nanogels consisting of a cross‐linked poly‐N‐isopropylacrylamide nanogel, copolymerised with a photocatalytically active monomer. The dual‐responsive polymer nanogels undergo a stark decrease in diameter with increasing temperature, which shields the photocatalytic sites, decreasing the activity. Temperature‐dependent photocatalytic formation of NAD+ in water demonstrates the ability to switch photocatalysis on and off. Moreover, the photocatalysed syntheses of several fine chemicals were carried out to demonstrate the utility of the designed material. 相似文献
Increasing recognition of the role of oxidative stress in the pathogenesis of many clinical conditions and the existence of defined redox potential in healthy tissues has led to extensive research in the development of redox‐responsive materials for biomedical applications. Especially, considerable growth has been seen in the fabrication of polymeric nanogel–based drug delivery carriers utilizing redox‐responsive cross‐linkers bearing a variety of functional groups via various synthetic strategies. Redox‐responsive polymeric nanogels provide an advantage of facile chemical modification post synthesis and exhibit a remarkable response to biological redox stimuli. Due to the interdisciplinary nature of the subject, a more profound combined conceptual knowledge from a chemical and biological point of view is imperative for the rational design of redox‐responsive nanogels. The present review provides an insight into the design and fabrication of redox‐responsive nanogels with particular emphasis on synthetic strategies utilized for the development of redox‐responsive cross‐linkers, polymerization techniques being followed for nanogel development and biomedical applications. Cooperative effect of redox trigger with other stimuli such as pH and temperature in the evolution of dual and triple stimuli‐responsive nanogels is also discussed. 相似文献
Here we report the preparation and characterization of nanostructured thermo-responsive poly(acrylamide) (PAM)-based hydrogels. The addition of slightly crosslinked poly(N-isopropylacrylamide) (PNIPA) nanogels to AM reactive aqueous solution produces nanostructured hydrogels that exhibit a volume phase transition temperature (TVPT). Their swelling kinetics, TVPT's and mechanical properties at the equilibrium-swollen state (Heq) are investigated as a function of the concentration of PNIPA nanogels in the nanostructured hydrogels. Nanostructured hydrogels with PNIPA nanogels/AM mass ratios of 20/80 and above exhibit higher Heq and longer time to reach the equilibrium swelling than those of the conventional PAM hydrogels. However, the PNIPA nanogels possess thermo-responsive character missing in conventional PAM hydrogels. The TVPT of nanostructured hydrogels depends on PNIPA nanogel content but their elastic and Young moduli are larger than those of conventional hydrogels at similar swelling ratios. Swelling kinetics, TVPT, and mechanical properties are explained in terms of the controlled in-homogeneities introduced by the PNIPA nanogels during the polymerization. 相似文献
Well‐defined nanogels have become quite attractive as safe and stable carriers for siRNA delivery. However, to avoid nanoparticle accumulation, they need to provide a stimuli‐responsive degradation mechanism that can be activated at the payload's site of action. In this work, the synthetic concept for generating well‐defined nanohydrogel particles is extended to incorporate disulfide cross‐linkers into a cationic nanonetwork for redox‐triggered release of oligonucleotide payload as well as nanoparticle degradation under reductive conditions of the cytoplasm. Therefore, a novel disulfide‐modified spermine cross‐linker is designed that both allows disassembly of the nanogel as well as removal of cationic charge from residual polymer fragments. The degradation process is monitored by scanning electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS). Moreover, siRNA release is analyzed by agarose gel electrophoresis and a fluorescent RNA detection assay. The results exemplify the versatility of the applied nanogel manufacturing process, which allows alternative stimuli‐responsive core cross‐linkers to be integrated for triggered oligonucleotide release as well as effective biodegradation for reduced nanotoxicity.