Synthesis and characterization of core–shell‐type polymeric micelles from diblock copolymers via reversible addition–fragmentation chain transfer

A method was developed to enable the formation of nanoparticles by reversible addition–fragmentation chain transfer polymerization. The thermoresponsive behavior of polymeric micelles was modified by means of micellar inner cores and an outer shell. Polymeric micelles comprising AB block copolymers of poly(N‐isopropylacrylamide) (PIPAAm) and poly(2‐hydroxyethylacrylate) (PHEA) or polystyrene (PSt) were prepared. PIPAAm‐b‐PHEA and PIPAAm‐b‐PSt block copolymers formed a core–shell micellar structure after the dialysis of the block copolymer solutions in organic solvents against water at 20 °C. Upon heating above the lower critical solution temperature (LCST), PIPAAm‐b‐PHEA micelles exhibited an abrupt increase in polarity and an abrupt decrease in rigidity sensed by pyrene. In contrast, PIPAAm‐b‐PSt micelles maintained constant values with lower polarity and higher rigidity than those of PIPAAm‐b‐PHEA micelles over the temperature range of 20–40 °C. Structural deformations produced by the change in the outer polymer shell with temperature cycles through the LCST were proposed for the PHEA core, which possessed a lower glass‐transition temperature (ca. 20 °C) than the LCST of the PIPAAm outer shell (ca. 32.5 °C), whereas the PSt core with a much higher glass‐transition temperature (ca. 100 °C) retained its structure. The nature of the hydrophobic segments composing the micelle inner core offered an important control point for thermoresponsive drug release and the drug activity of the thermoresponsive polymeric micelles. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3312–3320, 2006     

Preparation,morphology, and thermoresponsive properties of poly(N‐isopropylacrylamide)‐based copolymer microgels

In this research, thermoresponsive copolymer latex particles with an average diameter of about 200–500 nm were prepared via surfactant‐free emulsion polymerization. The thermoresponsive properties of these particles were designed by the addition of hydrophilic monomers [acrylic acid (AA) and sodium acrylate (SA)] to copolymerize with N‐isopropylacrylamide (NIPAAm). The effects of the comonomers and composition on the synthesis mechanism, kinetics, particle size, morphology, and thermoresponsive properties of the copolymer latex were also studied to determine the relationships between the synthesis conditions, the particle morphology, and the thermoresponsive properties. The results showed that the addition of hydrophilic AA or SA affected the mechanism and kinetics of polymerization. The lower critical solution temperature (LCST) of the latex copolymerized with AA rose to a higher temperature. However, because the strong hydrophilic and ionic properties of SA caused a core–shell structure, where NIPAAm was in the inner core and SA was in the outer shell, the LCST of the latex copolymerized with SA was still the same as that of pure poly(N‐isopropylacrylamide) latex. It was concluded that these submicrometer copolymer latex particles with different thermoresponsive properties could be applied in many fields. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 356–370, 2006     

Synthesis of a thermoresponsive shell‐crosslinked 3‐layer onion‐like polymer particle with a hyperbranched polyglycerol core

A novel thermoresponsive shell crosslinked three‐layer onion‐like polymer particles were prepared using hyperbranched polyglycerol (PG) as parents compound, the periphery hydroxyl groups of PG were transformed into trithiocarbonates (? SC(S)S? ) first; then, it was used as chain transfer agent to prepare star‐like block copolymer of N‐isopropyl acrylamide (NIPA) and N,N‐dimethylaminoethyl acrylate (DMA) in sequence via reversible addition fragmentation chain transfer (RAFT) process. Thus, a three‐layer polymer, PG? [SC(S)S? (DMA)? b? (NIPA)]_n, was obtained. The middle layer of poly(DMA) was then crosslinked with 1,8‐diiodoctane, and the resulting onion‐like three‐layer polymer showed a lower critical solution temperature (LCST) in water because of the outer layer of poly(NIPA). The LCST value only slightly depended on the crosslinking degree. Finally, the ? SC(S)S? were transformed into thiols by sequential treating with sodium borohydride and formic acid; thus, the core molecule was chemically detached from the crosslinked shell and a novel shell crosslinked polymer particle was obtained. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5652–5660, 2005     

Water‐soluble,thermoresponsive, hyperbranched copolymers based on PEG‐methacrylates: Synthesis,characterization, and LCST behavior

A series of water‐soluble thermoresponsive hyperbranched copoly(oligoethylene glycol)s were synthesized by copolymerization of di(ethylene glycol) methacrylate (DEG‐MA) and oligo(ethylene glycol) methacrylate (OEG‐MA, M_w = 475 g/mol), with ethylene glycol dimethacrylate (EGD‐MA) used as the crosslinker, via reversible addition fragmentation chain transfer polymerization. Polymers were characterized by size exclusion chromatography and nuclear magnetic resonance analyses. According to the monomer composition, that is, the ratio of OEG‐MA: DEG‐MA: EGD‐MA, the lower critical solution temperature (LCST) could be tuned from 25 °C to 90 °C. The thermoresponsive properties of these hyperbranched copolymers were studied carefully and compared with their linear analogs. It was found that molecular architecture influences thermoresponsive behavior, with a decrease of around 5–10 °C in the LCST of the hyperbranched polymers compared with the LCST of linear chains. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2783–2792, 2010     

Poly(ether tert‐amine): A novel family of multiresponsive polymer

A novel multiresponsive poly(ether tert‐amine) (PEA) was synthesized by nucleophilic addition/ring‐opening reaction of commercial poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO), and di‐epoxy and di‐amine monomer. The process of synthesis was very simple and green in ethanol as reactive media. These PEAs exhibit sharp response to temperature, pH, and ionic strength, with adjustable and sharp phase transitions in the range of 27–100 °C. The lower critical solution temperature (LCST) of PEA's aqueous solution presents a linear relationship to the PEO content (y = 35.7 + x), indicating well‐tunable LCST. The concentration of PEA has no obvious effect on LCST. Therefore, PEA will be potential in applications of drug delivery, separation, and biotechnology. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1292–1297, 2009     

Flocculation‐resistant multimolecular micelles with thermoresponsive corona from dendritic heteroarm star copolymers

In this article, we report the self‐assembly of flocculation‐resistant multimolecular micelles with thermoresponsive corona from novel dendritic heteroarm star copolymers. The micelles have a core‐shell‐corona structure at room temperature according to pyrene probe fluorescence spectrometry, proton nuclear magnetic resonance (¹H NMR), transmission electron microscopy, and dynamic light scattering measurements. Increasing the temperature above the lower critical solution temperature (LCST), the micelles show high flocculation‐resistant ability resulting from a structure transition from core‐shell‐corona to core‐shell confirmed by a quantitative variable temperature ¹H NMR analysis method using potassium hydrogen phthalate as an external standard. A big volume change of the micelles is observed during the LCST transition. The drug loading and temperature‐dependent release properties of the micelles are also investigated by using coumarin 102 as a model drug, which displays a rapid drug release at a temperature above the LCST. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Amphiphilic dendritic copolymers of tert‐butyl‐glycidylether and glycidol as a nanocontainer for an anticancer ruthenium complex

Dendritic copolymers comprising a hydrophobic core and hydrophilic shell with nearly equal numbers of hydroxyl groups in the shell and different densities in the core were prepared by a multi‐step process based on anionic ring‐opening polymerization. The diversity in the core density was obtained by using copolymer stars with poly(tert‐butyl‐glycidylether)‐block‐polyglycidol arms with nearly equal length of hydrophobic blocks and numbers of hydroxyl groups of polyglycidol but different numbers of arms as macroinitiators. The ability of the dendritic copolymers to serve as a nanocontainer for a ruthenium complex Ru(NH₃)₃Cl₃ with anticancer properties was studied. The possibility of improving the water solubility of this poorly soluble drug by loading it onto dendritic copolymers was investigated. The hydroxyl groups of the dendritic copolymers were used for complexation of the ruthenium compound to the shell. The loading efficiency was analyzed by UV–vis spectroscopy. The dendritic nanoparticles in their hydrated state were visualized using cryo‐TEM. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3488–3497     

Stimulus‐responsive polymers based on 2‐hydroxypropyl acrylate prepared by RAFT polymerization

Homopolymerization and diblock copolymerization of 2‐hydroxypropyl acrylate (HPA) has been conducted using reversible addition fragmentation chain transfer (RAFT) chemistry in tert‐butanol at 80 °C. PHPA homopolymers were obtained with high conversions and narrow molecular weight distributions over a wide range of target degrees of polymerization. Like its poly(2‐hydroxyethyl methacrylate) isomer, PHPA homopolymer exhibits inverse temperature solubility in dilute aqueous solution, with cloud points increasing systematically on lowering the mean chain length. The nature of the end groups is shown to significantly affect the cloud point, whereas no effect of concentration was observed over the PHPA concentration range investigated. Various thermoresponsive PHPA‐based diblock copolymers were prepared via one‐pot syntheses in which the second block was either permanently hydrophilic or pH‐responsive. Preliminary studies confirmed that poly(ethylene oxide)‐poly(2‐hydroxypropyl acrylate) (PEO₄₅‐PHPA₄₈) and poly(2‐hydroxypropyl acrylate)‐ poly(2‐hydroxyethyl acrylate) (PHPA₄₉‐PHEA₆₈)diblock copolymers formed well‐defined PHPA‐core micelles in 10 mM sodium nitrate solution at 40 °C and 70 °C with mean hydrodynamic diameters of 20 nm and 35 nm, respectively. In contrast, most other PHPA‐based diblock copolymers investigated formed larger colloidal aggregates in 10 mM NaNO₃ solution at elevated temperatures. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2032–2043, 2010     

Synthesis and self‐assembly of thermoresponsive poly(N‐isopropylacrylamide)‐b‐poly(oligo ethylene glycol methyl ether acrylate) double hydrophilic block copolymers

We report on the synthesis of novel poly(N‐isopropylacrylamide)‐b‐poly(oligo ethylene glycol methyl ether acrylate) (PNIPAM‐b‐POEGA) thermoresponsive block copolymers using reversible addition–fragmentation chain transfer polymerization methodologies. The synthesized block copolymers are characterized by gel permeation chromatography, nuclear magnetic resonance, Fourier transform infrared (FTIR) techniques in terms of molecular weight and composition. Their thermoresponsive self‐assembly in aqueous media is investigated using dynamic and static light scattering. The PNIPAM‐b‐POEGA thermoresponsive block copolymers formed aggregates in water by increasing the temperature above the lower critical solution temperature value of PNIPAM block. Solution pH seems to affect the self‐assembly behavior in some cases due to the presence of ? COOH end groups. Therefore, the copolymers were utilized as “smart” nanocarries for the hydrophobic drug indomethacin, implementing a novel encapsulation protocol taking advantage of the thermoresponsive character of the PNIPAM block. The empty and loaded self‐assembled nanocarriers systems were studied by light scattering techniques, ultraviolet–visible, and FTIR spectroscopy, which gave information on the size and structure of the nanocarriers, the drug loading content and the interactions between the drug and the components of the block copolymers. Drug loaded nanostructures show stability at room temperature, due to active drug/block copolymer interactions. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1467–1477     

Well‐defined thermoresponsive dendritic polyamide/poly(N‐vinylcaprolactam) block copolymers

The first‐ and second‐generation well‐defined thermoresponsive amphiphilic linear–dendritic diblock copolymers based on hydrophilic linear poly(N‐vinylcaprolactam) and hydrophobic dendritic aromatic polyamide have been synthesized via reversible addition fragmentation chain transfer polymerization of N‐vinylcaprolactam by employing dendritic chain‐transfer agents possessing a single dithiocarbamate moiety at the focal point. These linear–dendritic copolymers exhibit reversible temperature‐dependent phase transition behaviors in aqueous solution as characterized by turbidity measurements using UV–vis spectroscopy. Their lower critical solution temperatures depend on the generation of the dendritic aromatic polyamides and the concentrations of the copolymer solutions. These amphiphilic copolymers are able to form nanospherical micelles in the aqueous solution as revealed by fluorescent spectroscopy, dynamic light scattering, and transmission electron microscope (TEM). The core–shell structure of micelles has been proved by ¹H NMR analyses of the micelles in D2O. The micelles loaded with indomethacin as a model drug showed high‐drug loading capacity and thermoresponsive drug release behavior. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3240–3250     

Self‐assembly of amphiphilic ABA random triblock copolymers in water

Self‐assembly of amphiphilic ABA random triblock copolymers in water serves as a novel approach to create unique structure micelles connected with flexible linkages. The ABA triblock copolymers consist of amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) and hydrophobic dodecyl pendants as the A segments and a hydrophilic poly(ethylene oxide) (PEO) as the middle B segment. The A block is varied in dodecyl methacrylate content of 20%–50% and degree of polymerization (DP) of 100‐200. By controlling the composition and DP of the A block, various architectures can be tailor‐made as micelles in water: PEO‐linked double core unimer micelles, PEO‐looped unimer or dimer micelles, and multichain micelles. Those PEO‐linked or looped micelles further exhibit thermoresponsive solubility in water. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 313–321     

Biodegradable poly(carbonate‐ether)s with thermoresponsive feature at body temperature

Novel biodegradable poly(carbonate‐ether)s (PCEs) with lower critical solution temperature (LCST) at body temperature were synthesized by copolymerization of CO₂ and ethylene oxide (EO) under double metal cyanide (DMC) catalyst. The PCEs showed carbonate unit (CU) content of 1.0–42.4 mol % and molecular weight of 2.7–247 kg/mol, which exhibited reversible thermoresponsive feature in deionized water with LCST in a broad window from 21.5 to 84.1 °C. The LCST was highly sensitive to the CU content and the molecular weight of PCEs, and it showed a linear relation with CU content for PCEs with similar molecular weight. In particular, aqueous solution of PCE with a 26.0 mol % of CU showed an LCST around 36.1 °C, which was very close to the body temperature. Interestingly, it was found that the phase transition behavior changed with PCE concentration. For PCE with M_n of 2.7 kg/mol and CU content of 30.0 mol %, the LCST increased from 21.5 to 36.7 °C when the PCE concentration changed from 10 to 1 g/L. Dynamic light scattering indicated that the phase transition was possibly due to a coil‐to‐globule transition. The thermoresponsive biodegradable PCE with LCST at body temperature is promising for biomedical applications, especially for in vivo applications. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

The effect of structure on the thermoresponsive nature of well‐defined poly(oligo(ethylene oxide) methacrylates) synthesized by ATRP

Statistical copolymers of di(ethylene glycol) methyl ether methacrylate (MEO₂MA) and tri(ethylene glycol) methyl ether methacrylate (MEO₃MA) were synthesized by atom transfer radical polymerization (ATRP) providing copolymers with controlled composition and molecular weights ranging from M_n = 8,300–56,500 with polydispersity indexes (M_w/M_n) between 1.19 and 1.28. The lower critical solution temperature (LCST) of the copolymers increased with the mole fraction of MEO₃MA in the copolymer over the range from 26 to 52 °C. The average hydrodynamic diameter, measured by dynamic light scattering, varied with temperature above the LCST. These two monomers were also block copolymerized by ATRP to form polymers with molecular weight of M_n = 30,000 and M_w/M_n from 1.12 to 1.21. The LCST of the block copolymers shifted toward the LCST of the major segment, as compared to the value measured for the statistical copolymers at the same composition. As temperature increased, micelles, consisting of aggregated PMEO₂MA cores and PMEO₃MA shell, were formed. The micelles aggregated upon further heating to precipitate as larger particles. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 194–202, 2008     

Reactive surfactants in heterophase polymerization. XXV. Core–shell lattices stabilized with a mixture of maleic anionic and styrenic nonionic surfactants

Core–shell lattices with a polystyrene core and a polystyrene/butyl acrylate shell with more than 40% solid contents were produced using a combination of sodium dodecyl maleate hemiester as anionic surfactant and styrenic block copolymer of butylene oxide and ethylene oxide as nonionic surfactant. Stable lattices able to resist rather high concentrations of electrolytes can be obtained, provided a careful protocol of the addition of surfactants is used. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2251–2262, 1999     

Synthesis and Self‐Assembly of Thermoresponsive Amphiphilic Biodegradable Polypeptide/Poly(ethyl ethylene phosphate) Block Copolymers

We report the design and synthesis of new fully biodegradable thermoresponsive amphiphilic poly(γ‐benzyl L ‐glutamate)/poly(ethyl ethylene phosphate) (PBLG‐b‐PEEP) block copolymers by ring‐opening polymerization of N‐carboxy‐γ‐benzyl L ‐glutamate anhydride (BLG? NCA) with amine‐terminated poly(ethyl ethylene phosphate) (H₂N? PEEP) as a macroinitiator. The fluorescence technique demonstrated that the block copolymers could form micelles composed of a hydrophobic core and a hydrophilic shell in aqueous solution. The morphology of the micelles as determined by transmission electron microscopy (TEM) was spherical. The size and critical micelle concentration (CMC) values of the micelles showed a decreasing trend as the PBLG segment increased. However, UV/Vis measurements showed that these block copolymers exhibited a reproducible temperature‐responsive behavior with a lower critical solution temperature (LCST) that could be tuned by the block composition and the concentration.     

Thermoresponsive micelles from Jeffamine-b-poly(L-glutamic acid) double hydrophilic block copolymers

Double hydrophilic block copolymers (DHBC) consisting of a Jeffamine block, a statistical copolymer based on ethylene oxide and propylene oxide units possessing a lower critical solution temperature (LCST) of 30 degrees C in water, and poly(L-glutamic acid) as a pH-responsive block were synthesized by ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride using an amino-terminated Jeffamine macroinitiator, followed by hydrolysis. This DHBC proved thermoresponsive as evidenced by dynamic light scattering and small-angle neutron scattering experiments. Spherical micelles with a Jeffamine core and a poly(L-glutamic acid) corona were formed above the LCST of Jeffamine. The size of the core of such micelles decreased with increasing temperature, with complete core dehydration being achieved at 66 degrees C. Such behavior, commonly observed for thermosensitive homopolymers forming mesoglobules, is thus demonstrated here for a DHBC that self-assembles to generate thermoresponsive micelles of high colloidal stability.     

Selected‐Control Fabrication of Multifunctional Fluorescent–Magnetic Core–Shell and Yolk–Shell Hybrid Nanostructures

The selected‐control preparation of uniform core–shell and yolk–shell architectures, which combine the multiple functions of a superparamagnetic iron oxide (SPIO) core and europium‐doped yttrium oxide (Y₂O₃:Eu) shell in a single material with tunable fluorescence and magnetic properties, has been successfully achieved by controlling the heat‐treatment conditions. Furthermore, the shell thickness and interior cavity of SPIO@Y₂O₃:Eu core–shell and yolk–shell nanostructures can be precisely tuned. Importantly, as‐prepared SPIO@Y₂O₃:Eu yolk–shell nanocapsules (NCs) modified with amino groups as cancer‐cell fluorescence imaging agents are also demonstrated. To the best of our knowledge, this is the first report on the selected‐control fabrication of uniform SPIO@Y₂O₃:Eu core–shell nanoparticles and yolk–shell NCs. The combined magnetic manipulation and optical monitoring of magnetic–fluorescent SPIO@Y₂O₃:Eu yolk–shell NCs will open up many exciting opportunities in dual imaging for targeted delivery and thermal therapy.     

Synthesis and characterization of temperature‐sensitive block‐graft PNiPAAm‐b‐(PαN3CL‐g‐alkyne) copolymers by ring‐opening polymerization and click reaction

This study synthesized thermo‐sensitive amphiphilic block‐graft PNiPAAm‐b‐(PαN₃CL‐g‐alkyne) copolymers through ring‐opening polymerization of α‐chloro‐ε‐caprolactone (αClCL) with hydroxyl‐terminated macroinitiator poly(N‐isopropylacrylamide) (PNiPAAm), substituting pendent chlorides with sodium azide. This was then used to graft various kinds of terminal alkynes moieties by means of the copper‐catalyzed Huisgen's 1,3‐dipolar cycloaddition (“click” reaction). ¹H NMR, FTIR, and gel permeation chromatography (GPC) was used to characterize these copolymers. The solubility of the block‐graft copolymers in aqueous media was investigated using turbidity measurement, revealing a lower critical solution temperature (LCST) in the polymers. These solutions showed reversible changes in optical properties: transparent below the LCST, and opaque above the LCST. The LCST values were dependant on the composition of the polymer. With critical micelle concentrations (CMCs) in the range of 2.04–9.77 mg L^?1, the block copolymers formed micelles in the aqueous phase, owing to their amphiphilic characteristics. An increase in the length of hydrophobic segments or a decrease in the length of hydrophilic segments amphiphilic block‐graft copolymers produced lower CMC values. The research verified the core‐shell structure of micelles by ¹H NMR analyses in D₂O. Transmission electron microscopy was used to analyze the morphology of the micelles, revealing a spherical structure. The average size of the micelles was in the range of 75–145 nm (blank), and 105–190 nm (with drug). High drug entrapment efficiency and drug loading content were observed in the drug micelles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of superparamagnetic and thermoresponsive hybrid nanoparticles via surface‐mediated RAFT polymerization of di(ethylene glycol) ethyl ether acrylate and (oligoethylene glycol) methyl ether acrylate

A reversible addition‐fragmentation chain transfer (RAFT) agent was directly anchored onto superparamagnetic Fe₃O₄ nanoparticles (SPNPs) in a simple procedure using a ligand exchange reaction of 2‐[(dodecylsulfanylcarbonylthiolsulfanyl) propionic acid] (DCPA) with oleic acid initially present on the surface of Fe₃O₄ nanoparticles. The DCPA‐modified SPNPs were then used for the surface‐mediated RAFT polymerization of di(ethylene glycol) ethyl ether acrylate and (oligoethylene glycol) methyl ether acrylate to fabricate structurally well‐defined hybrid SPNPs with temperature‐responsive poly[di(ethylene glycol) ethyl ether acrylate‐co‐(oligoethylene glycol) methyl ether acrylate] shell and magnetic Fe₃O₄ core. Evidence of a well‐controlled surface‐mediated RAFT polymerization was gained from a linear increase of number‐average molecular weight with overall monomer conversions and relatively narrow polydispersity indices of the copolymers grown from the SPNPs. The resultant hybrid nanoparticles exhibited superparamagnetic property with a saturation magnetization of 55.1–19.4 emu/g and showed a temperature‐responsive phenomenon as the temperature changed between 25 and 40 ^°C. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3420–3428     

Dual Redox and Thermoresponsive Double Hydrophilic Block Copolymers with Tunable Thermoresponsive Properties and Self‐Assembly Behavior

The synthesis, tunable thermoresponsive properties, and self‐assembly of dual redox and thermoresponsive double hydrophilic block copolymers having pendant disulfide linkages (DHBCss) are reported. Well‐defined DHBCss composed of a hydrophilic poly(ethylene oxide) block and a dual thermo‐ and reduction‐responsive random copolymer block containing pendant disulfide linkages are synthesized by atom transfer radical polymerization. Their lower critical solution temperature (LCST) transitions are adjusted through modulating pendant hydrophobic–hydrophilic balance with disulfide–thiol–sulfide chemistry. Further, these DHBCss derivatives are converted to disulfide‐crosslinked nanogels at temperatures above LCST through temperature‐driven self‐assembly and in situ disulfide crosslinking. They exhibit enhanced colloidal stability and further reduction‐responsive degradability, thus demonstrating versatility of dual thermo‐ and reduction‐responsive smart materials.