PNIPAAm Block Research Articles

Polymer nanoparticles with a sensitive CO2‐responsive hydrophilic/hydrophobic surface

ABSTRACTPoly(methyl methacrylate) (PMMA) nanoparticles with a sensitive CO2‐responsive hydrophilic/hydrophobic surface that confers controlled dispersion and aggregation in water were prepared by emulsion polymerization at 50 °C under CO2 bubbling using amphiphilic diblock copolymers of 2‐dimethylaminoethyl methacrylate (DMAEMA) and N‐isopropyl acrylamide (NIPAAm) as an emulsifier. The amphiphilicity of the hydrophobic–hydrophilic diblock copolymer at 50 °C was triggered by CO2 bubbling in water and enabled the copolymer to serve as an emulsifier. The resulting PMMA nanoparticles were spherical, approximately 100 nm in diameter and exhibited sensitive CO2/N2‐responsive dispersion/aggregation in water. Using copolymers with a longer PNIPAAm block length as an emulsifier resulted in smaller particles. A higher concentration of copolymer emulsifier led to particles with a stickier surface. Given its simple preparation and reversible CO2‐triggered amphiphilic behavior, this newly developed block copolymer emulsifier offers a highly efficient route toward the fabrication of sensitive CO2‐stimuli responsive polymeric nanoparticle dispersions. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2149–2156

Synthesis of Thermosensitive Conjugated Triblock Copolymers by Sequential Click Couplings for Drug Delivery and Cell Imaging.

The elegant integration of an excellent light-emitting segment and a biorelevant signal-responsive moiety could generate advanced polymeric delivery systems with simultaneously favorable diagnostic and therapeutic functions with respect to cancer theranostics. Although polymeric delivery systems based on fluorescent polyfluorene (PF) or thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) have been extensively developed, the preparation of a ternary polymer formulation composed of a PF block, a PNIPAAm sequence, and a hydrophilic moiety remains rarely explored likely because of the difficulty in integrating different synthesis strategies for polymer synthesis. To this end, herein we reported the design and controlled synthesis of a PF- and PNIPAAm-based amphiphilic triblock copolymer, PF11-b-PNIPAAm120-b-poly(oligo(ethylene glycol) monomethyl ether methacrylate)17 (PF11-b-PNIPAAm120-b-POEGMA17), with a well-defined structure by a strategy of sequential click couplings between Suzuki-coupling-generated PF and atom-transfer radical polymerization (ATRP)-produced PNIPAAm and POEGMA. The as-prepared triblock copolymers can self-assemble into micelles with a core-shell-corona (CSC) structure that is composed of an inner hydrophobic core of the PF moiety for fluorescent tracking and drug encapsulation, a thermosensitive middle shell of PNIPAAm block for thermomodulated drug loading and release, and a hydrophilic outer corona of the POEGMA segment for micelle stabilization. Interestingly, the doxorubicin (DOX)-loaded micelles prepared at 25 °C had a greater drug loading capacity than the analogues fabricated at 37 °C due to the better stability of the former formulation, leading to its higher in vitro cytotoxicity in HeLa cells. Together with the integration of a localized hyperthermia-triggered drug release profile and efficiently intracellular trafficking of the nanocarriers by monitoring the fluorescence of the PF moiety, this formulation demonstrates a great potential for cancer theranostics.

Differences in self‐assembly features of thermoresponsive anionic triblock copolymers synthesized via one‐pot or two‐pot by atom transfer radical polymerization

ABSTRACTThe self‐assembly process in aqueous solutions of the methoxyl‐poly(ethylene glycol)‐block‐poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic sodium)‐block‐poly(N‐isopropyl acrylamide) (PNIPAAM) triblock copolymer, synthesized via two different atomic transfer radical polymerization methods, namely “one‐pot” (P3‐sample) and “two‐pot” (P2‐sample), was studied by various experimental techniques. The “one‐pot” procedure leads to a copolymer (P3) where the PNIPAAM block is contaminated with a minor quantity of 2‐acrylamido‐2‐methyl‐1‐propane sulfonate (AMPS) residuals and this sample does not form micelles over the considered temperature region, but unimers and temperature‐induced aggregates coexist in the presence of a small amount of salt. The P2 polymer forms micelles and intermicellar structures, but the former moieties disappear at high temperatures, whereas the latter species contract with increasing temperature. Small‐angle neutron scattering results revealed correlation peaks, both for P3 and P2, and no micelle formation for P3, but a pronounced upturn of the scattered intensity at low wavevector values at elevated temperatures for the P2 copolymer. The findings from this study clearly show that the spurious AMPS residuals have a drastic influence on the self‐assembly and micelle formation of the triblock copolymer. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 524–534

Synthesis of dual thermo- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid)-grafted cellulose nanocrystals by reversible addition-fragmentation chain transfer polymerization.

Free and cellulose nanocrystals (CNCs)-grafted block copolymers of acrylic acid and N-isopropylacrylamide with various poly(N-isopropylacrylamide) (PNIPAAm) block lengths as dual temperature- and pH-sensitive materials were synthesized by reversible addition-fragmentation chain transfer polymerization via an R-approach method. Controlling lower critical solution temperature (LCST) of the products by changing the PNIPAAm block length, addition of CNC, and variation of pH was studied. The free and CNC-grafted block copolymers were analyzed by Fourier transform infrared and proton nuclear magnetic resonance. LCST of copolymers was measured by dynamic light scattering using their hydrodynamic diameters. The block copolymers reversibly form core-corona structure with PNIPAAm as core and poly(acrylic acid) (PAA) as shell above LCST at higher pH values. LCST point shifts to higher temperatures by increasing pH and CNC content and also lowering PNIPAAm block length. By decreasing pH below 4 at certainly low temperatures, PAA becomes core and PNIPAAm forms corona. Thermal behavior of the CNC-grafted polymers was studied by thermal gravimetric analysis and differential scanning calorimetry. Morphology of the polymer-grafted CNC was examined by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 231-243, 2018.

Temperature and pH dual stimuli responsive PCL-b-PNIPAAm block copolymer assemblies and the cargo release studies

A new atom transfer radical polymerization (ATRP) initiator, namely, 2-(1-(2-azidoethoxy)ethoxy)ethyl 2-bromo-2-methylpropanoate containing both “cleavable” acetal linkage and “clickable” azido group was synthesized. Well-defined azido-terminated poly(N-isopropylacrylamide)s (PNIPAAm-N3)s with molecular weights and dispersity in the range 11,000–19,000 g mol−1 and 1.20–1.28, respectively, were synthesized employing the initiator by ATRP. Acetal containing PCL-b-PNIPAAm block copolymer was obtained by alkyne–azide click reaction of azido-terminated PNIPAAm-N3 with propargyl-terminated PCL. Critical aggregation concentration (CAC) of PCL-b-PNIPAAm copolymer in aqueous solution was found to be 8.99 × 10−6 M. Lower critical solution temperature (LCST) of PCL-b-PNIPAAm copolymer was found to be 32 °C which was lower than that of the precursor PNIPAAm-N3 (36.4 °C). The effect of dual stimuli viz. temperature and pH on size and morphology of the assemblies of PCL-b-PNIPAAm block copolymer revealed that the copolymer below LCST assembled in spherical micelles which subsequently transformed to unstable vesicles above the LCST. Heating these assemblies above 40 °C led to the precipitation of PCL-b-PNIPAAm block copolymer. Whereas, at decreased pH, micelles of PCL-b-PNIPAAm copolymer disintegrate due to the cleavage of acetal linkage and precipitation of hydrophobic hydroxyl-terminated PCL. The encapsulated pyrene release kinetics from the micelles of synthesized PCL-b-PNIPAAm copolymer was found to be faster at higher temperature and at lower pH. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 1383–1396

Synthesis, characterization, and solution behavior of well-defined double hydrophilic linear amphiphilic poly (N-isopropylacrylamide)-b-poly (ε-caprolactone)-b-poly (N-isopropylacrylamide) triblock copolymers

Well-defined linear dihydrophilic amphiphilic ABA-type triblock copolymers of e-caprolactone (CL) and N-isopropylacrylamide (NIPAAm) have successfully been synthesized with a high yield by combining the ring opening polymerization (ROP) and xanthate-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization methods. The resulted block copolymer shows the formation of micelles in water as supported by light scattering. The critical micelle concentration (cmc) value of the micelle increases with the increase in the chain length of the poly (N-isopropylacrylamide) (PNIPAAm) block. Cloud point of the block copolymers decreases with the decrease in the PNIPAAm chain length. The TGA analysis shows a one-step degradation and a lower thermal stability of the triblock copolymer than the PNIPAAm. The DSC analysis of the triblock copolymer shows the lowering of glass transition temperature (T g), and melting temperature (T m) peaks possibly due to the partial miscibility of the poly (e-caprolactone) (PCL) block with the amorphous PNIPAAm block through the interaction of ester groups of PCL with the amide groups of PNIPAAm. The XRD pattern of the triblock copolymer shows a broad peak due to the suppression of the crystallization of PCL block owing to the mixing of PNIPAAm block with the PCL block.

Ionic effects on the behavior of thermoresponsive PEO–PNIPAAm block copolymers

ABSTRACTThe temperature‐dependent aggregation and recovery of the copolymer poly(ethylene oxide)22‐b‐poly(N‐isopropylacrylamide)29 with a C12 end‐cap in aqueous solutions of salts and acids are investigated. Salt solutions affected the critical aggregation temperature of the copolymer in a manner predictable according to the Hofmeister series, with the kosmotropic adipic ion lowering the critical aggregation temperature and the chaotropic iodide raising it. Also, both salts and acids increased the size of copolymer aggregates formed with heating, due to the electrostatic shielding of aggregated structures provided by the electrolytes. Additionally, the presence of ionic additives caused a thermohysteretic increase in the size of copolymer aggregates with temperature cycling. The transitions of polymer structure with increasing temperature were surprisingly sharp with the C12 end‐cap present, and particularly broad in samples in which the end cap had been cleaved. This observation suggested that the hydrophobic end group was responsible for imparting some degree of order to the polymer at low temperatures, which allowed for rapid reconfiguration with increasing temperature. Finally, in addition to the transitions expected from the least critical solution temperature behavior of the polymer blocks, we have observed an unexpected additional transition which we attribute to the contraction of the poly(ethylene oxide) chains of the copolymer aggregates at higher temperatures. This work illustrates the importance of considering the environment and composition of thermoresponsive block copolymers in certain applications, particularly in solutions with even modest electrolyte concentrations (1–10 mM), as it can have a profound effect on transition temperatures and morphology. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 507–516

Tailoring the amphiphilicity and self-assembly of thermosensitive polymers: end-capped PEG-PNIPAAM block copolymers.

In this work we report on the synthesis and self-assembly of a thermo-sensitive block copolymer system of n-octadecyl-poly(ethylene glycol)-block-poly(N-isopropylacrylamide), abbreviated as C18-PEGn-b-PNIPAAMm. We present a facile synthetic strategy for obtaining highly tunable thermo-responsive block copolymers starting from commercial PEG-based surfactants (Brij®) or a C18 precursor and conjugating with PNIPAAM via an Atom Transfer Radical Polymerization (ATRP) protocol. The self-assembly and detailed nanostructure were thoroughly investigated in aqueous solutions using both small-angle X-ray and neutron scattering (SAXS/SANS) combined with turbidity measurements. The results show that the system forms rather well defined classical micellar structures at room temperature that first undergo a collapse, followed by inter-micellar aggregation upon increasing the temperature. For the pure C18-PNIPAAM system, however, rather ill-defined micelles were formed, demonstrating the important role of PEG in regulating the nanostructure and the stability. It is found that the PEG content can be used as a convenient parameter to regulate the thermoresponse, i.e., the onset of collapse and aggregation. A detailed theoretical modeling analysis of the SAXS/SANS data shows that the system forms typical core-shell micellar structures. Interestingly, no evidence of back folding, where PEG allows PNIPAAM to form part of the C18 core, can be found upon crossing the lower critical solution temperature (LCST). This might be attributed to the entropic penalty of folding a polymer chain and/or enthalpic incompatibility between the blocks. The results show that by appropriately varying the balance between the hydrophobic and hydrophilic content, i.e. the amphiphilicity, tunable thermoresponsive micellar structures can be effectively designed. By means of SAXS/SANS we are able to follow the response on the nanoscale. These results thus give considerable insight into thermo-responsive micellar systems and provide guidelines as to how these systems can be tailor-made and designed. This is expected to be of considerable interest for potential applications such as in nanomedicine where an accurate and tunable thermoresponse is required.

Influence of poly(ethylene glycol) block length on the adsorption of thermoresponsive copolymers onto gold surfaces

The adsorption of a series of four poly(N-isopropylacrylamide)-based copolymers composed of a hydrophilic block of methoxy poly(ethylene glycol) (MPEG) with a variable length and a PNIPAAM block of fixed size (MPEGn-b-PNIPAAM71) onto flat and spherical citrate-coated gold surfaces has been investigated. The adsorption onto planar surfaces was studied by means of the quartz crystal microbalance with dissipation monitoring, whereas polymer adsorption onto gold nanoparticles was examined using dynamic light scattering and visible spectroscopy. Experiments were performed with two different concentrations of polymer in bulk solution, namely 0.05 and 0.0005 wt%. The influence of the MPEG length on the thickness of the adsorbed layer on the nanoparticles, and the adsorbed mass onto the planar surfaces were recorded at different temperatures.

Temperature-responsive cationic block copolymers as nanocarriers for gene delivery

Cationic block copolymers have been regarded as promising alternatives to the use of viral vectors for gene delivery. In this work, poly(N-isopropylacrylamide)n-block-poly((3-acrylamidopropyl)trimethylammonium chloride)m (PNIPAAMn-b-PAMPTMA(+)m) block copolymers with n=48 or 65 and m=6, 10 or 20 were synthesized and evaluated in terms of their potential for in vitro transfection of HeLa cells. These block copolymers collapse above a phase transition temperature, allowing the entrapment of the DNA molecules they are adsorbed to. The transfection efficiency increased with polymer concentration and was higher in the presence of a long PNIPAAM block and for a short charged block. In general, increasing the length of the charged block decreased the transfection efficiency. Additionally, polymer-DNA complexes (polyplexes) formed at lower polymer/DNA charge ratios caused lower cell toxicity levels. All polymers were shown to efficiently protect the DNA, even when they were present at low concentrations. At 37°C, the polyplexes mostly formed structures with size ranging from 100 to 500nm. The results also showed that the thermoresponsive contraction of PNIPAAM causes the charged block segments to be pressed out to the surface. The formation of compact structures seems to be a key factor in achieving high transfection efficiency.

Effects of Temperature and Salt Addition on the Association Behavior of Charged Amphiphilic Diblock Copolymers in Aqueous Solution

Effects of temperature on the association behavior in aqueous solutions of a series of charged thermoresponsive poly(N-isopropylacrylamide)-block-poly((3-acrylamidopropyl) trimethylammonium chloride) (abbreviated as PNIPAAM(n)-b-PAMPTMA(+)(20)) with different lengths of the PNIPAAM block (n = 24, 48, and 65) have been studied with the aid of turbidimetry, zeta sizer, and dynamic light scattering (DLS). The turbidity results show that the transition to high turbidity values is shifted to lower temperatures when the length of the PNIPAAM block increases. It was observed that the value of the cloud point (CP) dropped with increasing polymer concentration, enlarged length of the PNIPAAM block, and augmented salinity. It was found that the decay of the correlation function from DLS is bimodal at temperatures well below CP, where the fast mode represents the motion of the unimers and the slow mode the dynamics of micelles/intermicellar complexes. At higher temperatures, larger particles of the system grow at the expense of the smaller ones in the spirit of Ostwald ripening, and clusters with a narrow size distribution evolve at high temperatures. By adding salt (NaCl), enhanced aggregation occurs at elevated temperatures because of screening of Coulomb repulsions.

“Schizophrenic” Hemocompatible Copolymers via Switchable Thermoresponsive Transition of Nonionic/Zwitterionic Block Self-Assembly in Human Blood

"Schizophrenic" diblock copolymers containing nonionic and zwitterionic blocks were prepared with well-controlled molecular weights via atom-transfer radical polymerization (ATRP). In this work, we report a systematic study of how morphological changes of poly(N-isopropylacrylamide)-block-poly(sulfobetaine methacrylate) (PNIPAAm-b-PSBMA) copolymers affect hemocompatibility in human blood solution. The "schizophrenic" behavior of PNIPAAm-b-PSBMA was observed by (1)H NMR, dynamic light scattering (DLS), and turbidity measurement with double morphological transition, exhibiting both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) in aqueous solution. Below the UCST of PSBMA block, micelles were obtained with a core of insoluble PSBMA association and a shell of soluble PNIPAAm, whereas the opposite micelle structure was observed above the LCST of PNIPAAm block. In between the UCST and LCST, unimers with both soluble blocks were detected. Hydrodynamic size of prepared polymers and copolymers is determined to illustrate the correlations between intermolecular nonionic/zwitterionic associations and blood compatibility of PNIPAAm, PNIPAAm-b-PSBMA, and PSBMA suspension in human blood. Human fibrinogen adsorption onto the PNIPAAm-b-PSBMA copolymers from single-protein solutions was measured by DLS to determine the nonfouling stability of copolymer suspension. The new nonfouling nature of PNIPAAm-b-PSBMA copolymers was demonstrated to show extremely high anticoagulant activity and antihemolytic activity in human blood over a wide range of explored temperatures from 4 to 40 °C. The temperature-independent blood compatibility of nonionic/zwitterionic block copolymer along with their schizophrenic phase behavior in aqueous solution suggests their potential in blood-contacting applications.

Effect of Charge Density Matching on the Temperature Response of PNIPAAM Block Copolymer–Gold Nanoparticles

Upon conjugation of thermoresponsive polymers to nanomaterials such as gold nanoparticles (Aunps), whether and to what extent the properties of the polymer-coated Aunps differ from that of the free...

Studies on Micellization Behavior of Thermosensitive PNIPAAm-b-PLA Amphiphilic Block Copolymers

Thermo-sensitive amphiphilic block copolymers, poly(N-isopropylacrylamide)-block- poly(D,L-lactide) (PNIPAAm-b-PLA), were synthesized through a simple free radical copolymerization route based on a bifunctional initiator, 2,2'-azobis(2-methylpropion amidine) dihydrochloride (AMAD), followed by the ring-opening polymerization of D,L-lactide in the presence of Sn(Oct)2 catalyst. The Chemical structure characterization were conducted by means of 1H NMR, FT-IR, GPC. The amphiphilic PNIPAAm-b-PLA block copolymers could self-assemble into micelles with regularly spherical shape in an aqueous solution, with a TEM diameter range of 46-56 nm, DLS hydrodynamic diameter of 158-199 nm. This behavior depends on the environmental temperature, the hydrophobic interactions among PNIPAAm molecular chains, intermolecular hydrogen bonding between the PNIPAAm chains and water molecules as well as intramolecular hydrogen bonding between -CONH2 groups. The copolymers held a CMC from 5.50 to 6.17 mg L(-1) and LCST from 31.41-32.03 degrees C, being more or less affected by their compositions, PLA or PNIPAAm block length. The as-prepared PNIPAAm-b-PLA block polymers are anticipated to be applied as a potential candidate of drug release carriers.

Assemblies of Thermoresponsive Diblock Copolymers: Micelle and Vesicle Formation Investigated by Means of Dielectric Relaxation Spectroscopy

The dielectric properties of aqueous solutions of two different thermoresponsive mixed copolymers, (3-acrylamidopropyl)trimethylammonium chloride and N-isopropylacrylamide, PAMPTMA-b-NIPAAM, and sodium 2-acrylamido-2-methylpropanesulfonate and N-isopropylacrylamide, PAMPS-b-PNIPAAM, have been investigated in the frequency range where marked interfacial polarization mechanisms occur, both below and above the lower critical solution temperature. In the presence of poly(ethylene oxide)-PNIPAAM block polymers, PEO-b-PNIPAAM, these classes of copolymers give rise to different types of aggregates with different compositions and different architectures. By the combined results from dielectric relaxation spectroscopy, dynamic light scattering, and ζ-potential measurements, we give evidence for assembling into two different composite structures, a core-shell-type micellar structure built up by a hydrophobic core surrounded by a hydrophilic charged layer, in the case of the PEO-b-PNIPAAM + PAMPS-b-PNIPAAM system, and a vesicular structure encompassing an aqueous core in the case of the PEO-b-PNIPAAM + PAMPTMA-b-PNIPAAM system. These different structures, governed by a delicate interplay between electrostatic and hydrophobic interactions, are characterized by dielectric parameters (dielectric increments and relaxation frequencies) that can be properly deduced from suitable dielectric models, in the framework of heterogeneous system theory. These structures and in particular hallow particles with a large internal aqueous core, where large hydrophilic compounds can be encapsulated, offer novel and interesting properties in biomedical technologies and in particular in drug delivery as drug mesoscopic carriers.

Structure and Interactions of Charged Triblock Copolymers Studied by Small-Angle X-ray Scattering: Dependence on Temperature and Charge Screening

A series of thermo-responsive cationic triblock copolymers composed of methoxy-poly(ethylene glycol) (MPEG, hydrophilic), poly(N-isopropylacrylamide) (PNIPAAM, temperature sensitive), and poly((3-acrylamidopropyl) trimethyl ammonium chloride) (PN(+), cationic) has been investigated as a function of temperature and ionic strength. In the MPEG-b-PNIPAAM-b-PN(+) copolymers, the MPEG block length is constant, and the lengths of the PNIPAAM and PN(+) blocks are varied. The solubility of the PNIPAAM block decreases with increasing temperature, and the triblock copolymer thus provides the possibilities of studying micelles with both neutral and charged blocks in the micelle corona as well as the interplay between these two blocks as the electrostatic interactions are varied by addition of salt. Investigation of the systems by densitometry and small-angle X-ray scattering (SAXS) in a temperature range from 20 to 70 °C gave detailed information on the behavior both below and above the critical micelle temperature (CMT). A clear effect of the addition of salt is observed in both the apparent partial specific volume, obtained from the densitometry measurements, and the SAXS data. Below the CMT, the single polymers can be described as Gaussian chains, for which the repulsive interchain interactions, originating from the charged PN(+) block, have to be taken into account in salt-free aqueous solution. Increasing the salt concentration of the solution to 30 mM NaCl leads to an increase in the apparent partial specific volume, and the electrostatic repulsive interchain interactions between the single polymers vanish. Raising the temperature results in micelle formation, except for the copolymer with only 20 NIPAAM units. The SAXS data show that the polymer with the medium PNIPAAM block length forms spherical micelles, whereas the polymer with the longest PNIPAAM block forms cylindrical micelles. Increasing the temperature further above the CMT results in an increase in the micellar aggregation number for both of the polymers forming spherical and cylindrical micelles. The addition of salt to the solution also influences the aggregates formed above the CMT. Overall, the micelles formed in the salt solution have a smaller cross-section radius than those in aqueous solution without added salt.

Synthesis and micellization of thermosensitive PNIPAAm-b-PLA amphiphilic block copolymers based on a bifunctional initiator

The thermo-sensitive amphiphilic block copolymer poly(N-isopropylacrylamide)-block-poly(D,L-lactide) (PNIPAAm-b-PLA) was synthesized using a simple free radical copolymerization route based on a bifunctional initiator, 2,2-azobis(2-methylpropion amidine) dihydrochloride followed by the ring-opening polymerization of D,L-actide in the presence of a Sn(Oct)2 catalyst. The chemical structure of the PNIPAAm-b-PLA copolymers was verified using Fourier transform-infrared spectrophotometry and nuclear magnetic resonance, and the molecular weight and polydispersity index were examined using gel permeation chromatography. The amphiphilic PNIPAAm-b-PLA block copolymers could self-assemble into spherically shaped micelles in an aqueous solution with a transmission electron microscopy diameter range of 40–56 nm and a dynamic laser scattering hydrodynamic diameter of 90–200 nm. This behavior depends on the environmental temperature, the hydrophobic interactions among PNIPAAm molecular chains, the intermolecular hydrogen bonding between the PNIPAAm chains and water molecules, and the intramolecular hydrogen bonding between the -CONH2 groups. The copolymers held a critical micellization concentration of 4.93–7.21 mg·L−1 and a low critical solution temperature of 31.15–32.62 °C being more or less affected by their compositions, PLA or PNIPAAm block length, and polymerization temperature. The as-prepared PNIPAAm-b-PLA block polymers are anticipated to be applied as candidate drug release carriers.

Effects of Temperature and Salt Concentration on the Structural and Dynamical Features in Aqueous Solutions of Charged Triblock Copolymers

Effects of temperature and salt addition on the association behavior in aqueous solutions of a series of charged thermosensitive methoxypoly(ethylene glycol)-block-poly(N-isopropylacrylamide)-block-poly(4-styrenesulfonic acid sodium) triblock copolymers (MPEG(45)-b-P(NIPAAM)(n)-b-P(SSS)(22)) with different lengths of the PNIPAAM block (n=17, 48, and 66) have been studied with the aid of turbidity, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS). Increasing temperature and salinity as well as longer PNIPAAM blocks are all factors that promote the formation of association structures. The SAXS data show that, for the copolymers with n=48 and n=66, increasing temperature and salt concentration induce interchain associations and higher values of the aggregation number, whereas no aggregation was observed for the copolymer with the shortest PNIPAAM chain. However, DLS measurements reveal the presence of larger association clusters. The cloud point is found to decrease with raising salinity and longer PNIPAAM block. The general picture that emerges is the delicate interplay between repulsive electrostatic forces and hydrophobic interactions and that this balance can be tuned by changing the temperature, salinity, and the length of the PNIPAAM block.

Effect of polyethylene glycol (PEG) length on the association properties of temperature-sensitive amphiphilic triblock copolymers (PNIPAAMm-b-PEGn-b-PNIPAAMm) in aqueous solution

Effects of temperature on the association behavior in aqueous solutions of a series of thermosensitive poly(N-isopropylacrylamide)-block-poly(ethylene glycol)-block-poly(N-isopropylacrylamide) triblock copolymers (PNIPAAMm-b-PEGn-b-PNIPAAMm) with the length of the PNIPAAM block fixed (m ≈ 67) and with different lengths of the PEG block (n = 23, 34, 77, and 165) have been studied with the aid of turbidity, dynamic light scattering (DLS), and Monte Carlo simulations. The turbidity results show that the sharp transition to high turbidity values is shifted to higher temperatures when the length of the PEG spacer is increased from 23 to 77, whereas no transition is observed for the longest PEG block. These findings are consistent with the DLS results, which suggest the formation of large association structures at temperatures well above the cloud point. The simulation results indicate that a long PEG-block portion separating the PNIPAAM blocks in the triblock copolymer reduces the tendency of the polymer forming interchain associations at elevated temperatures. Simulation shows that for a long PEG spacer, the copolymer moiety is rather extended even at high temperatures, whereas for copolymers with a short PEG length the thermoresponsive block copolymer undergoes a transition from an extended to a compact conformation.

Mixed Stimuli-Responsive Magnetic and Gold Nanoparticle System for Rapid Purification, Enrichment, and Detection of Biomarkers

A new diagnostic system for the enrichment and detection of protein biomarkers from human plasma is presented. Gold nanoparticles (AuNPs) were surface-modified with a diblock copolymer synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. The diblock copolymer contained a thermally responsive poly(N-isopropylacrylamide) (pNIPAAm) block, a cationic amine-containing block, and a semi-telechelic PEG₂-biotin end group. When a mixed suspension of 23 nm pNIPAAm-modified AuNPs was heated with pNIPAAm-coated 10 nm iron oxide magnetic nanoparticles (mNPs) in human plasma, the thermally responsive pNIPAAm directed the formation of mixed AuNP/mNP aggregates that could be separated efficiently with a magnet. Model studies showed that this mixed nanoparticle system could efficiently purify and strongly enrich the model biomarker protein streptavidin in spiked human plasma. A 10 ng/mL streptavidin sample was mixed with the biotinylated pNIPAAm-modified AuNPs and magnetically separated in the mixed nanoparticle system with pNIPAAm mNPs. The aggregates were concentrated into a 50-fold smaller fluid volume at room temperature where the gold nanoparticle reagent redissolved with the streptavidin target still bound. The concentrated gold-labeled streptavidin could be subsequently analyzed directly using lateral flow immunochromatography. This rapid capture and enrichment module thus utilizes the mixed stimuli-responsive nanoparticle system to achieve concentration of a gold-labeled biomarker that can be directly analyzed using lateral flow or other rapid diagnostic strategies.