Project description:We report a novel responsive supramolecular copolymer able to change its monomer sequence as a result of molecular stimuli. Nucleic acids and RNAse are used as molecular inputs, controlling the clustering of specific monomers along the polymer backbone. This opens new ways towards the molecular control of synthetic supramolecular networks.
Project description:In this study, we synthesized amphiphilic poly(2,7⁻(9,9⁻dioctylfluorene))⁻block⁻N,N⁻(diisopropylamino)ethyl methacrylate (POF⁻b⁻PDPMAEMA) rod-coil diblock copolymers by atom transfer radical polymerization (ATRP). The structure and multifunctional sensing properties of these copolymers were also investigated. The POF rod segment length of 10 was fixed and the PDPAEMA coil segment lengths of 90 and 197 were changed, respectively. The micellar aggregates of POF10⁻b⁻PDPAEMA90 rod-coil diblock copolymer in water showed a reversible shape transition from cylinder bundles to spheres when the temperature was changed from 20 to 80 °C or the pH was changed from 11 to 2. The atomic force microscopy (AFM) and transmission electron microscopy (TEM) measurements indicated that the temperature had also an obvious influence on the micelle size. In addition, since POF10⁻b⁻PDPAEMA90 had a lower critical solution temperature, its photoluminescence (PL) intensity in water is thermoreversible. The PL spectra showed that the POF⁻b⁻PDPAEMA copolymer had a reversible on/off profile at elevated temperatures, and thus could be used as an on/off fluorescent indicator for temperature or pH. The fluorescence intensity distribution of pH switched from "off⁻on" to "on⁻off" as the temperature increased. These results showed that the POF⁻b⁻PDPAEMA copolymer has a potential application for temperature and pH sensing materials.
Project description:An amphiphilic block copolymer (BCP) which contains both photoresponsive and thermoresponsive blocks was synthesized by the atom transfer radical polymerization approach. Meanwhile, a new core/shell type of the upconversion nanoparticle (UCNP) LiYF4:Yb3+ 0.25,Tm3+ 0.01@LiYF4:Yb3+ 0.2 was successfully synthesized. By encapsulating UCNPs inside the micelles of the BCP and incorporating Nile red (NR) into the UCNP@BCP hybrid nanoparticles as a model drug, controlled release of the drug by the dual-stimuli BCP could be studied. After exposing the UCNP-loaded micellar solution to near-infrared (NIR) light, it was found that the UV light pumped from UCNPs could disrupt the polymer micelles and the fluorescence intensity of NR decreased with the increase of the irradiation time of the NIR light. The thermoresponsive study indicated that the fluorescence intensity of NR decreased with the increase of temperature of the micellar solution because of the release of NR into water arising from the contraction of the amphiphilic BCP.
Project description:Polymerization-induced self-assembly (PISA) is used for the highly convenient and efficient preparation of ampholytic diblock copolymer nanoparticles directly in acidic aqueous solution. Cationic nanoparticles comprising a protonated polyamine stabilizer block and a hydrophobic polyacid core-forming block are formed at pH 2. Micelle inversion occurs at pH 10 to produce anionic nanoparticles with an ionized polyacid stabilizer block and a hydrophobic polyamine core-forming block. Macroscopic precipitation occurs at around pH 6-7, which lies close to the isoelectric point of this ampholytic diblock copolymer. Incorporation of fluorescein and rhodamine dye labels into the acid and amine blocks, respectively, leads to dual-color bifluorescent self-reporting pH-responsive nanoparticles.
Project description:Stimuli-responsive nanoparticles are among the most popular research topics. In this study, two types of core-shell (polystyrene with a photoiniferter (PSV) as the core and diblock as the shell) polymer brushes (PSV@PNIPA-b-PAA and PSV@PAA-b-PNIPA) were designed and prepared using surface-initiated photoiniferter-mediated polymerization (SI-PIMP). Moreover, their pH- and temperature-stimuli responses were explored by dynamic light scattering (DLS) and turbidimeter under various conditions. The results showed that the conformational change was determined on the basis of the competition among electrostatic repulsion, hydrophobic interaction, hydrogen bonding, and steric hindrance, which was also confirmed by protein adsorption experiments. These results are not only helpful for the design and synthesis of stimuli-responsive polymer brushes but also shed light on controlled protein immobilization under mild conditions.
Project description:IntroductionIntracellular delivery is a key step for many applications in medicine and for investigations into cellular function. This is particularly true for immunotherapy, which often requires controlled delivery of antigen and adjuvants to the cytoplasm of immune cells. Due to the complex responses generated by the stimulation of diverse immune cell populations, it is critical to monitor which cells are targeted during treatment. To address this issue, we have engineered an immunotheranostic polymersome delivery system that fluorescently marks immune cells following intracellular delivery.MethodsN-(3-bromopropyl)phthalimide end-capped poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-PPS-PI) was synthesized by anionic ring opening polymerization and linked with PEG-PPS-NH2 via a perylene bisimide (PBI) bridge to form a tetrablock copolymer (PEG-PPS-PBI-PPS-PEG). Block copolymers were assembled into polymersomes by thin film hydration in phosphate buffered saline and characterized by dynamic light scattering, cryogenic electron microscopy and fluorescence spectroscopy. Polymersomes were injected subcutaneously into the backs of mice, and draining lymph nodes were extracted for flow cytometric analysis of cellular uptake and disassembly.ResultsModular self-assembly of tetrablock / diblock copolymers in aqueous solutions induced π-π stacking of the PBI linker that both red-shifted and quenched the PBI fluorescence. Reactive oxygen species within the endosomes of phagocytic immune cell populations oxidized the PPS blocks, which disassembled the polymersomes for dequenching and shifting of the PBI fluorescence from 640 nm to 550 nm emission. Lymph node resident macrophages and dendritic cells were found to increase in 550 nm emission over the course of 3 days by flow cytometry.ConclusionsImmunotheranostic polymersomes present a versatile platform to probe the contributions of specific cell populations during the elicitation of controlled immune responses. Flanking PBI with two oxidation-sensitive hydrophobic PPS blocks enhanced π stacking and introduced a mechanism for disrupting π-π interactions to shift PBI fluorescence in response to oxidative conditions. Shifts from red (640 nm) to green (550 nm) fluorescence occurred in the presence of physiologically relevant concentrations of reactive oxygen species and could be observed within phagocytic cells both in vitro and in vivo.
Project description:Poly(N-vinylpyrrolidone) (PNVP) is a well-known, highly polar, nonionic water-soluble polymer. However, N-vinylpyrrolidone (NVP) usually exhibits strongly non-ideal behavior when copolymerized with methacrylic or styrenic monomers. Moreover, NVP is not particularly well-controlled under living radical polymerization conditions. For these reasons, alternative pyrrolidone-based monomers have been investigated. For example, the reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(N-methacryloyloxy)ethylpyrrolidone (NMEP) has been recently investigated using various polymerization formulations. However, PNMEP homopolymers are significantly less hydrophilic than PNVP and exhibit inverse temperature solubility in aqueous solution. In the present work, we studied the RAFT aqueous solution polymerization of 2-(N-acryloyloxy)ethylpyrrolidone (NAEP) using either AIBN at 70 °C or a low-temperature redox initiator at 30 °C. PNAEP homopolymers are obtained in high yield (>99%) with good control (M w/M n < 1.20) for target degrees of polymerization (DP) of up to 400 using the latter initiator, which produced relatively fast rates of polymerization. However, targeting DPs above 400 led to lower NAEP conversions and broader molecular weight distributions. 2-Hydroxyethyl acrylate (HEA) and oligo(ethylene glycol) methyl ether acrylate (OEGA) were chain-extended using a PNAEP x macro-CTA via RAFT aqueous solution polymerization, yielding double-hydrophilic acrylic diblock copolymers with high conversions (>99%) and good control (M w/M n < 1.31). In addition, a PNAEP95 macro-CTA was chain-extended via RAFT aqueous solution polymerization of N-isopropylacrylamide (NIPAM) at 22 °C. Dynamic light scattering (DLS) analysis indicated that heating above the lower critical solution temperature of PNIPAM led to so-called "anomalous micellization" at 35 °C and the formation of near-monodisperse spherical micelles at 40 °C. Finally, 2-(diethylamino)ethyl methacrylate (DEA) was polymerized using an N-morpholine-functionalized trithiocarbonate-based RAFT chain transfer agent and subsequently chain-extended using NAEP to form a novel pH-responsive diblock copolymer. Above the pK a of PDEA (∼7.3), DLS and 1H NMR studies indicated the formation of well-defined PDEA-core spherical micelles.
Project description:We report on a therapeutic approach using thermo-responsive multi-fingered drug eluting devices. These therapeutic grippers referred to as theragrippers are shaped using photolithographic patterning and are composed of rigid poly(propylene fumarate) segments and stimuli-responsive poly(N-isopropylacrylamide-co-acrylic acid) hinges. They close above 32 °C allowing them to spontaneously grip onto tissue when introduced from a cold state into the body. Due to porosity in the grippers, theragrippers could also be loaded with fluorescent dyes and commercial drugs such as mesalamine and doxorubicin, which eluted from the grippers for up to seven days with first order release kinetics. In an in vitro model, theragrippers enhanced delivery of doxorubicin as compared to a control patch. We also released theragrippers into a live pig and visualized release of dye in the stomach. The design of such tissue gripping drug delivery devices offers an effective strategy for sustained release of drugs with immediate applicability in the gastrointestinal tract.
Project description:Dynamic covalent chemistry (DCvC) has emerged as a versatile synthetic tool for devising stable, stimuli-responsive linkers or conjugates. The interplay of binding affinity, association and dissociation constants exhibits a strong influence on the selectivity of the reaction, the conversion rate, as well as the stability in aqueous solutions. Nevertheless, dynamic covalent interactions often exhibit fast binding and fast dissociation events or vice versa, affecting their conversion rates or stabilities. To overcome the limitation in linker design, we reported herein dual responsive dynamic covalent peptide tags combining a pH responsive boronate ester with fast association and dissociation rates, and a redox-active disulfide with slow formation and dissociation rate. Precoordination by boronic acid-catechol interaction improves self-sorting and selectivity in disulfide formation into heterodimers. The resulting bis-peptide conjugate exhibited improved complex stability in aqueous solution and acidic tumor-like extracellular microenvironment. Furthermore, the conjugate responds to pH changes within the physiological range as well as to redox conditions found inside cancer cells. Such tags hold great promise, through cooperative effects, for controlling the stability of bioconjugates under dilution in aqueous media, as well as designing intelligent pharmaceutics that react to distinct biological stimuli in cells.
Project description:Untethered small actuators have various applications in multiple fields. However, existing small-scale actuators are very limited in their intractability with their surroundings, respond to only a single type of stimulus and are unable to achieve programmable structural changes under different stimuli. Here, we present a multiresponsive patternable actuator that can respond to humidity, temperature and light, via programmable structural changes. This capability is uniquely achieved by a fast and facile method that was used to fabricate a smart actuator with precise patterning on a graphene oxide film by hydrogel microstamping. The programmable actuator can mimic the claw of a hawk to grab a block, crawl like an inchworm, and twine around and grab the rachis of a flower based on their geometry. Similar to the large- and small-scale robots that are used to study locomotion mechanics, these small-scale actuators can be employed to study movement and biological and living organisms.