In order to precisely tail the endocytosis process and determine the internal location of drug carriers in cells, fluorescent tracers with high sensitivity and versatility are one of the most powerful tools. Nevertheless, conventional single fluorescent probes always suffered from the interference of background fluorescence or the lack of long-time monitoring capability, resulting in the low resolution and efficiency. To overcome this drawback, nanocarriers capable of multicolor fluorogenic and ratiometric properties became an urgently needed solution. In this contribution, starting from pentafluorophenyl ester (PFP)- and tetraphenylethene (TPE)-functionalized phenyl isocyanide (PI) monomers as well as l-hydrophilic (HP) PI monomers, a type of well-defined amphiphilic block copolymer, P(PFPPI-co-TPEPI-co-HPPI)-b-HPPPI, with controlled molecular weights and tunable compositions was prepared through sequential living copolymerization with phenylethynyl Pd(II) complex as a single catalyst in one pot. Disulfide bonds were then introduced by the exchange reaction between PFP units and cystamine (Cys; a degradable cross-linker). The resultant P(CysPI-co-TPEPI-co-HPPI)-b-HPPPI copolymers showed a time-dependent disruption in the conditions mimicking the intracellular reducing environment and an aggregation-caused quenching (ACQ) optical behavior that they were emissive when single chain dispersed but became nonfluorescent if the polymer chains were aggregated. Thanks to such a unique optical phenomenon, nanocarriers capable of fluorescence ratiometric property could be constructed after incorporating another solvatochromic dye, Nile red (NR), in water. This new class of core cross-linked NR@P(CysPI-co-TPEPI-co-HPPI)-b-HPPPI micelles not only exhibited excellent fluorescence ratiometric cell imaging ability but also possessed rapid cell membrane permeability due to the PEGylated single left-handed helical PPI corona and exposed the real-time disintegration of nanocarriers in front of us. Fatal and irreversible damage to cancer cells could be achieved by the high-efficiency delivery of chemotherapeutic agents. We speculate that these newly developed fluorescent integrated nanocarriers can potentially be utilized as a promising approach to cancer diagnosis and therapy.

The use of proteins as therapeutics in nanomedicine is an emerging research field and has developed rapidly. However, proteins are always vulnerable to renal excretion or digestion by the proteolytic system in vivo, which limits their usage to a large extent. Although biocompatible polymers have been covalently linked to proteins to protect them from recognition by the immune system and prolong their circulation time, the biological activity of them is sometimes decreased. To fill this gap, physical isolation, wrapping, or encapsulation techniques are employed. Up to now, various mature examples were reported, but the whole time scales for guest molecules loading and releasing, especially the initial rapid loading process, were rarely mentioned. Herein, a series of dual-responsive poly(N-isopropylacrylamide-co-methacrylic acid) (P(NIPAM-co-MAA)) microgels were synthesized and employed to investigate the kinetics of in situ complexation and release of lysozyme under external stimuli modulation upon a stopped-flow apparatus, which was suitable for rapid dynamic monitoring. Close inspection of the adsorption kinetics during the early stages (< 50 s) revealed that the initial microgel collapse occurred within ~1 s, with more rapid transitions being observed when higher lysozyme concentrations were targeted. All the dynamic traces could be well fitted with a double exponential function, suggesting a fast (τ1) and a slow (τ2) relaxation time, respectively. Then, the kinetics of releasing bound lysozyme from microgels was carried on by utilizing the pH-responsive property, and the evaluation of the activity of released lysozyme was synchronously measured in a Micrococcus lysodeikticus (M. lysodeikticus) cell suspension. The corresponding relaxation time (τ) was also calculated by fitting the recorded dynamic traces. We speculate that this work can provide basic dynamics data and theoretical basis for microgels based nanocarriers to be used for protein delivery, controlled release, and possible chemical separation.

Aggregation-induced emission (AIE) active tetraphenylethene (TPE) functionalized phenyl isocyanide (PI) derivatives, such as TPE pendent PI monomers (TPE-NC) and TPE-based Pd(II) catalysts (TPE-Cat. a and TPE-Cat. b) were synthesized. The corresponding linear (poly(TPE-NC)n) and four-armed (TPE-[poly(TPE-NC)m]4) conjugated polymers were subsequently prepared through the living polymerization of TPE-NC with TPE-Cat. a or TPE-Cat. b in THF, respectively. All of them have good solubility in common organic solvents, such as THF and CHCl3, and exhibited tunable AIE property, which can be facilely tuned through the variations on the concentration and the molecular weights (MWs) of the polymers. They also showed excellent thermal stability with a 5% of their weight loss as high as 380–405 °C and significant mass loss in the range of 350–650 °C. Stable helical assemblies could be formed by poly(TPE-NC)n at high concentration conditions. However, four-armed TPE-[poly(TPE-NC)m]4 could self-assemble into an apparent bumpy “caterpillar” like assembly, which was very different from the ordinary ones. Moreover, these conjugated polymers could be employed to generate a vapochromism phenomenon and act as good dispersants for carbon agglomerates in poor solvents. It is expected that this work can enrich the family of luminescent materials based on the helical poly(phenyl isocyanide) main chains and guide the future design of optical materials with attractive structures and special purposes, such as heat-resistant materials, security materials, and dispersed materials.

Polymeric assemblies are distinguished by ease of preparation, high drug-loading content, and long circulation time compared to small molecular, making them quite promising for cancerous diagnosis and therapy. However, the therapeutic efficacy of traditional nanocarriers with random coil surface is always proved to be less effective because of the existence of several systemic and cellular barriers or the low tissue penetration from nanocarrier itself. To fill this gap, we report a new class of oxidation and pH dual-responsive amphiphilic triblock copolymer: poly(l-lactic acid)(-IR780)-b-hydrophobic poly(phenyl isocyanide)-b-hydrophilic poly(phenyl isocyanide) (PLLA(-IR780)-HBPPI-HPPPI). In neutral aqueous solution, the copolymers could form onion-like spherical micelles with diameter of ∼84 nm and consisting of PEGylated single left-handed helical PPI corona, endowing them rapid cell membrane permeability and internalization (10–20 min) that had an analogous effect of cell penetrating peptides (CPPs). Moreover, the phenylboronic pinacol ester contained in the hydrophobic interlayer was stable under neutral and weak acid milieu and thus could minimize the premature drug leakage and systemic cytotoxicity. Upon exposure to H2O2, the interlayer was oxidized rapidly and accompanied by a hydrophobic–hydrophilic transition, which resulted in the releasing of encapsulated drugs and creating interconnected hydrophilic channels to the inner PLLA core at the same time. An enhanced drug release from PLLA core was then achieved by the acid-triggered micelle degradation. The degradation rates of micelles and release rates of drugs could be easily tuned by changing the concentration of H2O2 and the acidity. The hyperthermia induced by the micelles could increase to as high as ∼48 °C upon near-infrared (NIR) light irradiation (808 nm, 1 W cm–2) due to the introduction of NIR absorptive IR780 dyes. Combined with the effect of chemotherapeutics, fatal and irreversible damage to cancer cells was observed. The primary objective of this research was to address the growing need for an effective/rapid drug delivery system and programmed/sustained on-demand drug release. We speculate that the newly developed multifunctional integrated micelles with combined advantages can potentially be utilized as a promising approach to disease diagnosis and therapy.

A facile construction of diverse polymeric nanostructures was reported by simple quaternization reaction and UV irradiation starting from the same rod–rod conjugated poly(4-isocyano-benzoic acid 5-(2-dimethylamino-ethoxy)-2-nitro-benzyl ester)-b-poly(3-hexylthiophene) (PPI(-DMAENBA)-b-P3HT) diblock copolymers, which were prepared by sequential living copolymerization of 4-isocyano-benzoic acid tert-butyl ester (PI) and 3-hexylthiophene (3HT) using Ni(dppp)Cl2 as a catalyst in a one-pot process with a subsequent chemical modification. The facile quaternization reaction and UV irradiation upon PPI(-DMAENBA)-b-P3HT could afford quaternized PPI(-DMAENBA)-b-P3HT (PPI(-QDMAENBA)-b-P3HT) and poly(4-isocyano-benzoic acid)-b-poly(3-hexylthiophene) (PPI(-AA)-b-P3HT) copolymers. Two different polymeric micellar supramolecular structures with cationic and anionic surface properties could be obtained by direct dispersion of positively charged PPI(-QDMAENBA)-b-P3HT and negatively charged PPI(-AA)-b-P3HT copolymers into water. Interestingly, the resultant PPI(-QDMAENBA/DMAENBA)-b-P3HT block copolymers with a 40% degree of quaternization were found to exhibit unique light emissions with the color transformed from luminous yellow to pink depending on the solvent ratio of THF and water used. An almost neutral and ordered thin film was achieved on the exact stoichiometric charge balance between these two types of oppositely charged micelles, which highlights the potential to incorporate conjugated copolymers into the assembled block copolymer micelles (BCMs) to yield multifunctional ordered films and relevant applications.

We report a new type of functional composite films by taking advantage of the interface-directed assembly between thiol groups functionalized poly(4-isocyano benzoic acid⋯pyridine-4-thiol)-b-poly(3-hexylthiophene) (PPI(–SH)-b-P3HT) conjugated copolymers and gold nanoparticles (Au NPs) at the chloroform/water interface. The PPI(–SH)-b-P3HT copolymers were synthesized through hydrogen bonding induced micellization and subsequent thiol–disulfide exchange reaction. Transmission electron microscopic (TEM) and atomic force microscopy (AFM) observations showed the film was uniform on a large scale and the integrity of surface morphology was not affected by the Au NPs concentration. Interestingly, the film substrate not only exhibited a strongly Au NPs concentration dependent surface-enhanced Raman scattering (SERS) activity but also allowed detection of model molecule, IR-792 perchlorate (IR-792), in the SERS measurement. This proof-of-concept suggests the interfacial assembly route is effective in integrating the properties of organic polymers and inorganic nanoparticles, and for further application.

We report on the preparation of a well-defined star-shaped tricationic ionic liquid possessing three arms of poly(ethylene glycol) functionalized imidazolium rings. Remarkable solubility was found in most of the organic solvents we used. Thermogravimetric analysis (TGA) exhibited excellent thermal stability and two distinct decomposition temperatures were attributed to two kinds of chemical degradation. Differential scanning calorimetry (DSC) was further employed to investigate the thermal phase transitions, that three different signals (Tg, Tc, and Tm) were shown upon the second heating process. Moreover, CH2Cl2 solution of the ionic liquid expressed an excitation-wavelength dependent fluorescence response, leading to the facile modulation of photoluminescence behavior. This work represents an example of utilizing molecular design to construct novel ionic liquids and endow further potential to be used in the engineering materials.

A family of well-defined poly(3-hexylthiophene)-b-poly(5,8-di-p-tolylquinoxaline-2,3-diyl) rod–rod block copolymers was designed and synthesized in one pot via mechanistically distinct, sequential living polymerization using Ni(dppp)Cl2 as a single catalyst. The block copolymerization was demonstrated to proceed in a living/controlled chain-growth manner, affording the desired block copolymers in high yields with tunable compositions, controlled molecular weight, and narrow molecular weight distributions. The resulting block copolymer was revealed to self-assemble into various well-defined supramolecular structures depending on the solvents used such as nano-fibril and spherical nanoparticles. Very interestingly, such a block copolymer displayed highly selective visual detection for cobalt over most other competing metal ions by changing its orange color to light green and bright orange emission to deep green. The detection limit was estimated to be down to 1.0 × 10−7 M and the interference of the other competing metal ions is negligible. Furthermore, such a block copolymer can be applied using test strips, making it a practical, sensitive, and selective probe for cobalt ions.

We report on the fabrication of a class of surface-enhanced Raman scattering (SERS) active thermometers, which consists of 60 nm gold nanoparticles, encoded with Raman-active dyes, and a layer of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brush with different chain lengths. These SERS-active nanoparticles can be optimized to maintain spectrally silent when staying as single particles in dispersion. Increasing temperature in a wide range from 25 °C to 55 °C can reversibly induce the interparticle self-aggregation and turn on the SERS fingerprint signals with up to 58-fold of enhancement by taking advantage of the interparticle plasmonic coupling generated in the process of thermo-induced nanoparticles self-aggregation. Moreover, the most significative point is that these SERS probes could maintain their response to temperature and present all fingerprint signals in the presence of a colored complex. However, the UV-vis spectra can distinguish the differences faintly and the solution color shows little change in such complex mixture. This proof-of-concept and Raman technique applied here allow for dynamic SERS platform for onsite temperature detection in a wide temperature range and offer unique advantages over other detection schemes.

A variety of slightly cross-linked poly(2-vinylpyridine)–poly(N-isopropylacrylamide) (P2VP–PNIPAM) core–shell microgels with pH- and temperature-responsive characteristic were prepared via seeded emulsion polymerization. Negatively charged sodium 2,6-naphthalenedisulfonate (2,6-NDS) could be internalized into the inner core, followed by formation of (P2VPH+/SO32–) supramolecular complex through the electrostatic attractive interaction in acid condition. The thermoresponsive characteristic feature of the (P2VPH+/SO32–)–PNIPAM core–shell microgels was investigated by laser light scattering and UV–vis measurement, revealing an integration of upper critical solution temperature (UCST) and lower critical solution temperature (LCST) behaviors in the temperature range of 20–55 °C. The UCST performance arised from the compromised electrostatic attractive interaction between P2VPH+ and 2,6-NDS at elevated temperatures, while the subsequent LCST transition is correlated to the thermo-induced collapse of PNIPAM shells. The controlled release of 2,6-NDS was monitored by static fluorescence spectra as a function of temperature change. Moreover, stopped-flow equipped with a temperature-jump accessory was then employed to assess the dynamic process, suggesting a millisecond characteristic relaxation time of the 2,6-NDS diffusion process. Interestingly, the characteristic relaxation time is independent of the shell cross-link density, whereas it was significantly affected by shell thickness. We believe that these dual thermoresponsive core–shell microgels with thermotunable volume phase transition may augur promising applications in the fields of polymer science and materials, particularly for temperature-triggered release.

We report on the construction of a polyelectrolyte-responsive system evolved from sterically stabilized protonated poly(2-vinylpyridine) (P2VPH+) microgels. Negatively charged sodium dodecylbenzenesulfonate (SDBS) surfactants could be readily internalized into the cationic microgels by means of electrostatic interactions, resulting in microgel collapse and concomitant formation of surfactant micellar domains (P2VPH+/SDBS)-contained electrostatic complexes. These internal hydrophobic domains conferred the opportunity of fluorescent dyes to be loaded. The obtained fluorescent microgel complexes could be further disintegrated in the presence of anionic polyelectrolyte, poly(sodium 4-styrenesulfonate) (PNaStS). The stronger electrostatic attraction between multivalent P2VPH+ microgels and PNaStS polyelectrolyte than single-charged surfactant led to triggered release of the encapsulated pyrene dyes from the hydrophobic interiors into microgel dispersion. The process was confirmed by laser light scattering (LLS) and fluorescence measurements. Furthermore, the entire dynamic process of PNaStS adsorption into P2VPH+ microgel interior was further studied by stopped-flow equipment as a function of polyelectrolyte concentration and degree of polymerization. The whole adsorption process could be well fitted with a double-exponential function, suggesting a fast (τ1) and a slow (τ2) relaxation time, respectively. The fast process (τ1) was correlated well with the approaching of PNaStS with P2VPH+ microgel to form a nonequilibrium complex within the microgel shell, while the slow process (τ2) was consistent with the formation of equilibrium complexes in the microgel deeper inside. This simple yet feasible design augurs well for the promising applications in controlled release fields.