Thermally Stable and Chemically Recyclable Poly(ketal-ester)s Regulated by Floor Temperature.

Chemical recycling to monomers (CRM) offers a promising closed-loop approach to transition from current linear plastic economy toward a more sustainable circular paradigm. Typically, this approach has focused on modulating the ceiling temperature (Tc) of monomers. Despite considerable advancements, polymers with low Tc often face challenges such as inadequate thermal stability, exemplified by poly(γ-butyrolactone) (PGBL) with a decomposition temperature of ∼200 °C. In contrast, floor temperature (Tf)-regulated polymers, particularly those synthesized via the ring-opening polymerization (ROP) of macrolactones, inherently exhibit enhanced thermodynamic stability as the temperature increases. However, the development of those Tf regulated chemically recyclable polymers remains relatively underexplored. In this context, by judicious design and efficient synthesis of a biobased macrocyclic diester monomer (HOD), we developed a type of Tf -regulated closed-loop chemically recyclable poly(ketal-ester) (PHOD). First, the entropy-driven ROP of HOD generated high-molar mass PHOD with exceptional thermal stability with a Td,5% reaching up to 353 °C. Notably, it maintains a high Td,5% of 345 °C even without removing the polymerization catalyst. This contrasts markedly with PGBL, which spontaneously depolymerizes back to the monomer above its Tc in the presence of catalyst. Second, PHOD displays outstanding closed-loop chemical recyclability at room temperature within just 1 min with tBuOK. Finally, copolymerization of pentadecanolide (PDL) with HOD generated high-performance copolymers (PHOD-co-PPDL) with tunable mechanical properties and chemical recyclability of both components.

Enabling Closed-Loop Circularity of "Non-Polymerizable" α, ß-Conjugated Lactone Towards High-Performance Polyester with the Assistance of Cyclopentadiene.

Chemical recycling of polymers to monomers presents a promising solution to the escalating crisis associated with plastic waste. Despite considerable progress made in this field, the primary efforts have been focused on redesigning new monomers to produce readily recyclable polymers. In contrast, limited research into the potential of seemingly "non-polymerizable" monomers has been conducted. Herein, we propose a paradigm that leverages a "chaperone"-assisted strategy to establish closed-loop circularity for a "non-polymerizable" α, ß-conjugated lactone, 5,6-dihydro-2H-pyran-2-one (DPO). The resulting PDPO, a structural analogue of poly(δ-valerolactone) (PVL), exhibits enhanced thermal properties with a melting point (Tm) of 114 °C and a decomposition temperature (Td,5%) of 305 °C. Notably, owing to the structural similarity between DPO and δ-VL, the copolymerization generates semi-crystalline P(DPO-co-VL)s irrespective of the DPO incorporation ratio. Intriguingly, the inherent C=C bonds in P(DPO-co-VL)s enable their convenient post-functionalization via Michael-addition reaction. Lastly, PDPO was demonstrated to be chemically recyclable via ring-closing metathesis (RCM), representing a significant step towards the pursuit of enabling the closed-loop circularity of "non-polymerizable" lactones without altering the ultimate polymer structure.

Synthesis and antibacterial properties of fluorinated biodegradable cationic polyesters.

Antimicrobial peptide-mimicking antibacterial polymers represent a practical strategy to conquer the ever-growing threat of antimicrobial resistance. Herein, we report the syntheses and antibacterial performance of degradable amphiphilic cationic polyesters containing pendent quaternary ammonium motifs and hydrophobic alkyl or fluoroalkyl groups. These polyesters were conveniently prepared from poly(3-methylene-1,5-dioxepan-2-one) via highly efficient one-pot successive thiol-Michael addition reactions. The antibacterial activity of these polyesters against S. aureus and E. coli and their hemolytic activity toward red blood cells were evaluated; some of them showed moderate antibacterial activity and selectivity against Gram-positive S. aureus. The membrane disruption mechanism of these cationic polyesters was briefly explored by monitoring the bacteria killing kinetics and SEM observations. Moreover, the effects of cationic/hydrophobic ratio and the incorporation of fluoroalkyl groups on the antibacterial activity and selectivity of the polyesters were demonstrated.

Fully Bio-based Poly(ketal-ester)s by Ring-opening Polymerization of a Bicylcic Lactone from Glycerol and Levulinic Acid.

A fully renewable bio-based bicyclic lactone containing a five-membered cyclic ketal moiety, 7-methyl-3,8,10-trioxabicyclo[5.2.1]decan-4-one (TOD), was synthesized through a two-step acid-catalyzed process from glycerol and levulinic acid. The ring-opening polymerization (ROP) of TOD at 30°C with benzyl alcohol (BnOH) as the initiator and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as the catalyst can afford high molar mass PTOD with a cis-2.4-disubstitued 2-methyl 1,3-dioxolane moiety in its repeating unit. PTOD is an amorphous polymer with a glass transition temperature (Tg ) of 13°C. It can be hydrolyzed into structurally defined small molecules under acidic or basic conditions by the selective cleavage of either the cyclic ketal or the ester linkage respectively. The TBD-catalyzed copolymerization of L-lactide (L-LA) and TOD at -20°C was investigated. It was confirmed that L-LA polymerized quickly with racemization to form PLA, followed by a slow incorporation of TOD into the formed PLA chains via transesterification. By varying the feed ratios of L-LA to TOD, a series of random copolymers (PLA-co-PTOD) with different TOD incorporation ratios and tunable Tg s were obtained. Under acidic conditions, PLA-co-PTOD degrades much faster than PLA via the selective cleavage of the cyclic ketal linkages. This work provides insights for the development of more sustainable and acid-accelerated degradable alternatives to aliphatic polyesters.

Alternating [1.1.1]Propellane-(Meth)Acrylate Copolymers: A New Class of Dielectrics with High Energy Density for Film Capacitors.

Polymer dielectrics with high energy density are of urgent demand in electric and electronic devices, but the tradeoff between dielectric constant and breakdown strength is still unsolved. Herein, the synthesis and molar mass control of three alternating [1.1.1]propellane-(meth)acrylate copolymers, denoted as P-MA, P-MMA, and P-EA, respectively, are reported. These copolymers exhibit high thermal stability and are semi-crystalline with varied glass transition temperatures and melting temperatures. The rigid bicyclo[1.1.1]pentane units in the polymer backbone promote the orientational polarization of the polar ester groups, thus enhancing the dielectric constants of these polymers, which are 4.50 for P-EA, 4.55 for P-MA, and 5.11 for P-MMA at 10 Hz and room temperature, respectively. Moreover, the high breakdown strength is ensured by the non-conjugated nature of bicyclo[1.1.1]pentane unit. As a result, these copolymers show extraordinary energy storage performance; P-MA exhibits a discharge energy density of 9.73 J cm-3 at 750 MV m-1 and ambient temperature. This work provides a new type of promising candidates as polymer dielectrics for film capacitors, and offers an efficient strategy to improve the dielectric and energy storage properties by introducing rigid non-conjugated bicyclo[1.1.1]pentane unit into the polymer backbone.

Synthesis and Post-Functionalization of Poly(conjugated ester)s Based on 3-Methylene-1,5-dioxepan-2-one.

Poly(α-methylene ester)s are an attractive type of functional aliphatic polyesters that represent a platform for the fabrication of various biodegradable and biomedical polymers. Herein, we report the controlled ring-opening polymerization (ROP) of a seven-membered α-methylene lactone (3-methylene-1,5-dioxepan-2-one, MDXO) that was synthesized based on the Baylis-Hillman reaction. The chemoselective ROP of MDXO was catalyzed by diphenyl phosphate (DPP) at 60 °C or stannous octoate (Sn(Oct)2) at 130 °C, generating α-methylene-containing polyester (PMDXO) with a linear structure and easily tunable molar mass. The ring-opening copolymerization of MDXO with ε-caprolactone or 1,5-dioxepan-2-one was also performed under the catalysis of DPP or Sn(Oct)2 to afford copolymers with different compositions and sequence structures that are influenced by the kinds of monomers and catalysts. PMDXO is a slowly crystallizable polymer with a glass transition temperature of ca. -33 °C, and its melting temperature and enthalpy are significantly influenced by the thermal history. The thermal properties of the copolymers are dependent on their composition and sequence structure. Finally, the post-modification of PMDXO based on the thiol-Michael addition reaction was briefly explored using triethylamine as a catalyst. Given the optimized condition, PMDXO could be dually modified to afford biodegradable polyesters with different functionalities.

Fluoride-Triggered Self-Degradation of Poly(2,4-disubstitued 4-hydroxybutyric acid) Derivatives.

Self-immolative polymers are a special kind of degradable polymers that depolymerize into small molecules through a cascade of reactions upon stimuli-triggered cleavage of the polymer chain ends. This work reports the design and synthesis of a fluoride-triggered self-immolative polyester. A 2,4-disubstitued 4-hydroxy butyrate is first confirmed to quickly cyclize in solution to form a γ-butyrolactone derivative. Then, the Passerini three component reaction (P-3CR) of an AB dimer (A: aldehyde, B: carboxylic acid) with tert-butyl isocyanide or oligo(ethylene glycol) isocyanide affords two poly(2,4-disubstitued 4-hydroxybutyrate) derivatives (P2 and P3). Two silyl ether end-capped polymers (P4 and P5) are abtained from P2 and P3, and their degradation in solution is examined by NMR spectrum and size exclusion chromatography. Polymers P4 and P5 are stable in the absence of tetrabutylammonium fluoride (TBAF), while in the presence of TBAF, the molar masses of P4 and P5 gradually decrease with time together with the increase of the amount of formed 2,4-disubstitued γ-butyrolactone. The depolymerization mechanism is proposed. The first step is the fast removal of the silyl ether by fluoride. Then, the released hydroxyl group initiates the quick head-to-tail depolymerization of the polyester via intramolecular cyclization.

Redox-Responsive Fluorescent Polycarbonates Based on Selenide for Chemotherapy of Triple-Negative Breast Cancer.

Transient increase of reactive oxygen species (ROS) is vital for some physiological processes, whereas the chronic and sustained high ROS level is usually implicated in the inflammatory diseases and cancers. Herein, we report the innovative redox-responsive theranostic micellar nanoparticles that are able to load anticancer drugs through coordination and hydrophobic interaction and to fluorescently monitor the intracellular redox status. The nanoparticles were formed by the amphiphilic block copolymers composed of a PEG segment and a selenide-containing hydrophobic polycarbonate block with a small fraction of coumarin-based chromophore. Under the alternative redox stimulation that might be encountered in the physiological process of some healthy cells, these nanoparticles underwent the reversible changes in size, morphology, and fluorescence intensity. With the assistance of small model compounds, we clarified the chemistry behind these changes, that is, the redox triggered reversible transformation between selenide and selenoxide. Upon the monotonic oxidation similar to the sustained high ROS level of cancer cells, the nanoparticles could be disrupted completely, which was accompanied by the drastic decrease in fluorescence. Cisplatin and paclitaxel were simultaneously coloaded in the nanoparticles with a moderate efficacy, and the coordination between selenide and platinum improved the stability of the drug-loaded nanoparticles against dilution. The naked nanoparticles are cytocompatible, whereas the dual drug-loaded nanoparticles exhibited a concentration dependent and synergistic cytotoxicity to triple-negative breast cancer (TNBC) cells. Of importance, the drug-loaded nanoparticles are much more toxic to TNBC cells than to normal cells due in part to ROS overproduction in the former cell lines.

ROS-Responsive Chalcogen-Containing Polycarbonates for Photodynamic Therapy.

Reactive oxygen species (ROS)-responsive polymers have attracted attention for their potential in photodynamic therapy. Herein, we report the ROS-responsive aliphatic polycarbonates prepared by the ring-opening polymerization (ROP) of three six-membered cyclic carbonate monomers with ethyl selenide, phenyl selenide or ethyl telluride groups. Under catalysis of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), all three monomers underwent the controlled anionic ROP, showing a feature of equilibrium polymerization due to the bulky effect of 5,5-disubstituents. With PEG macroinitiator, three series amphiphilic block copolymers were prepared. They could form spherical nanoparticles of ∼100 nm, which were stable in neutral phosphate buffer but dissociated rapidly under triggering of H2O2. We studied the H2O2-induced oxidation profiles of selenide- or telluride-containing small molecules by 1H NMR and revealed the factors that affect the oxidation kinetics and products. On this basis, the oxidative degradation mechanism of the copolymer nanoparticles has been clarified. Under the same oxidative condition, the telluride-containing nanoparticle degraded with the fastest rate while the phenyl selenide-based one degraded most slowly. These ROS-responsive nanoparticles could load photosensitizer chlorin e6 (Ce6) and anticancer drug doxorubicin (DOX). Under red light irradiation, Ce6-sensitized production of 1O2 that triggered the degradation of nanoparticles, resulting in an accelerated payload release. In vitro cytotoxicity assays demonstrate that the nanoparticles coloaded with DOX and Ce6 exhibited a synergistic cell-killing effect to MCF-7 cells, representing a novel responsive nanoplatform for PDT and/or chemotherapy.

ROS-Activated Ratiometric Fluorescent Polymeric Nanoparticles for Self-Reporting Drug Delivery.

Reactive oxygen species (ROS)-responsive theranostic nanomedicines have attracted wide interest in recent years because ROS stress is implicated in some pathological disorders such as inflammatory diseases and cancers. In this article, we report a kind of innovative ROS-responsive theranostic polymeric nanoparticles that are able to load hydrophobic drugs and to fluorescently self-report the in vitro or intracellular drug release under ROS triggering. The fluorescent nanoparticles were formed by amphiphilic block copolymers consisting of a poly(ethylene glycol) (PEG) segment and an oxidation-responsive hydrophobic block. The copolymers with different hydrophobic block lengths were synthesized by the atom transfer radical polymerization of a phenylboronic ester-containing acrylic monomer with a small fraction of a ROS-activatable 1,8-naphthalimide-based fluorescent monomer, using PEG-Br as the macroinitiator. The copolymer nanoparticles were stable in neutral phosphate buffer but degraded upon H2O2 triggering, with the degradation rate depending on the hydrophobic block length and the concentration of H2O2. The degradation of nanoparticles was accompanied by a colorimetric change of the fluorophore from blue to green, which affords the nanoparticles the ability to detecting H2O2 by a ratiometric fluorescent approach. Moreover, the nanoparticles could encapsulate doxorubicin (DOX) and the H2O2-triggered DOX release was well associated with the change in ratiometric fluorescence. Confocal laser scanning microscope results reveal that the fluorescent nanoparticles were internalized into A549 cells through the endocytosis pathway. The ROS-stimulated degradation of the nanoparticles and intracellular DOX release and the fate of the degraded polymers could be monitored by ratiometric fluorescent imaging. Finally, the naked nanoparticles and the degradation products are cytocompatible, whereas the DOX-loaded ones exhibit concentration-dependent cytotoxicity. Of importance, the stimulation with exogenous H2O2 or lipopolysaccharide enhanced obviously the cell-killing capability of the DOX-loaded nanoparticles because of the ROS-enhanced intracellular DOX release.

Synthesis and pH-dependent hydrolysis profiles of mono- and dialkyl substituted maleamic acids.

Maleamic acid derivatives as weakly acid-sensitive linkers or caging groups have been used widely in smart delivery systems. Here we report on the controlled synthetic methods to mono- and dialkyl substituted maleamic acids and their pH-dependent hydrolysis behaviors. Firstly, we studied the reaction between n-butylamine and citraconic anhydride, and found that the ratio of the two n-butyl citraconamic acid isomers (α and ß) could be finely tuned by controlling the reaction temperature and time. Secondly, we investigated the effects of solvent, basic catalyst, and temperature on the reaction of n-butylamine with 2,3-dimethylmaleic anhydride, and optimized the reaction conditions to efficiently synthesize the dimethylmaleamic acids. Finally, we compared the pH-dependent hydrolysis profiles of four OEG-NH2 derived water-soluble maleamic acid derivatives. The results reveal that the number, structure, and position of the substituents on the cis-double bond exhibit a significant effect on the pH-related hydrolysis kinetics and selectivity of the maleamic acid derivatives. Interestingly, for the mono-substituted citraconamic acids (α-/ß-isomer), we found that their hydrolyses are accompanied by the isomerization between the two isomers.

Oxidation-Responsive Aliphatic Polycarbonates from N-Substituted Eight-Membered Cyclic Carbonate: Synthesis and Degradation Study.

Oxidation-responsive aliphatic polycarbonates represent a promising branch of functional biodegradable polymers. This paper reports the synthesis and ring-opening polymerization (ROP) of an eight-membered cyclic carbonate possessing phenylboronic pinacol ester (C3) and the H2 O2 -triggered degradation of its polymer (PC3). C3 is prepared from the inexpensive and readily available diethanolamine with a moderate yield and undergoes the well-controlled anionic ROP with a living character under catalysis of 1,8-diazabicyclo[5.4.0]undec-7-ene. It can also be copolymerized with l-lactide, trimethylene carbonate, and 5-ter-butyloxycarbonylamino trimethylene carbonate, affording the copolymers with a varied distribution of the repeating units. To clearly demonstrate the oxidative degradation mechanism of PC3, this paper first investigates the H2 O2 -induced decomposition of small-molecule model compounds by proton nuclear magnetic resonance (1 H NMR). It is found that the adduct products formed by the in-situ-generated secondary amines and p-quinone methide (QM) are thermodynamically unstable and can decompose slowly back to QM and the amines. On this basis, this paper further studies the H2 O2 -accelerated degradation of PC3 nanoparticles that are prepared by the o/w emulsion method. A sequential process of oxidation of the phenylboronic ester, 1,6-elimination of the in-situ-generated phenol, releasing CO2 and intramolecular cyclization or isomerization is proposed as the degradation mechanism of PC3.

Supersensitive Oxidation-Responsive Biodegradable PEG Hydrogels for Glucose-Triggered Insulin Delivery.

Reactive oxygen species (ROS)-responsive polymers and hydrogels represent an emerging family of intelligent materials owing to the key functions of ROS in physiological processes or pathological diseases. Nonetheless, the weaknesses such as low sensitivity, slow response, instability, and low mechanical strength are associated with the limited ROS-responsive polymeric or supramolecular hydrogels. In this study, a novel type of oxidation-responsive degradable hydrogels was fabricated by the redox-initiated radical polymerization of a 4-arm-poly(ethylene glycol) (PEG) acrylic macromonomer that possesses a H2O2-cleavable phenylboronic acid linker in each of the arms. The macroscopic hydrogels have the features of good cytocompatibility, moderate mechanical strength, and fast response toward H2O2 of low concentration, owing to the covalently cross-linked hydrophilic PEG network and high sensitivity of the linker. They could encapsulate biomacromolecules, such as insulin and glucose oxidase (GOx), with high efficacy, affording a new glucose-responsive insulin-delivery platform on the basis of enzymatic transformation of a biochemical signal (glucose) into an oxidative stimulus (H2O2). Interestingly, in vitro results demonstrate that the same GOx-loaded hydrogel exhibited disparate degradation modes under different triggering molecules, that is, bulk degradation by H2O2 and surface erosion by glucose. Moreover, compared to the macroscopic hydrogel, the nanogel with a diameter of ∼160 nm prepared by inverse emulsion polymerization showed a much higher degradation rate even under triggering of 20 µM H2O2, a pathologically available concentration in vivo.

Facile Synthesis of H2O2-Cleavable Poly(ester-amide)s by Passerini Multicomponent Polymerization.

We report the straightforward synthesis of two types of H2O2-cleavable poly(ester-amide)s (P1 and P2) via the Passerini multicomponent polymerization (P-MCP) of 4-formylbenzeneboronic acid pinacol ester with 1,6-diisocyanohexane and 1,6-hexanedioic acid or a polyethylene glycol (PEG) dicarboxylic acid. The H2O2-cleavable phenylboronic acid ester was integrated into the polymer backbone by the in situ formed benzyl ester bond. GPC and 1H NMR confirmed the complete H2O2-triggered degradation of these polymers in aqueous medium by a mechanism of sequential oxidation of phenylboronic acid ester and self-immolative elimination. Compared with the hydrophobic polymer P1, the PEG-based water-soluble polymer P2 degraded much faster even at a lower H2O2 concentration. Cytocompatible nanoparticles of polymer P1 loaded with fluorescent Nile red were fabricated, and controlled release of Nile red in response to H2O2 was achieved, thus, demonstrating the utility of these polymers as potential H2O2-responsive delivery vehicles.

Dual Sequence Control of Uniform Macromolecules through Consecutive Single Addition by Selective Passerini Reaction.

The selective Passerini reactions of 4-formylbenzoic acid and 4-isocyanobenzoic acid with aliphatic isocyanides and aldehydes were utilized to synthesize sequence-defined uniform macromolecules. Our strategy does not involve any protecting groups or reactive group transformation steps and allows direct and consecutive propagation of sequence in each step. Introduction of diverse side groups by using different aliphatic components provided a range of sequence-defined uniform macromolecules in high yield and gram scale. The strategy also allows further Passerini self-coupling or cross-coupling of the formed sequences with other small molecules, affording polymers with up to 5098.3 Da and 20 side groups. Thus, this strategy will show promise for more efficient synthesis of new sequence-defined macromolecules.

Oxidation-Responsive Polymer-Drug Conjugates with a Phenylboronic Ester Linker.

Polymer-drug conjugates have attracted great interest as one category of various promising nanomedicines due to the advantages of high drug-loading capacity, negligible burst release, and improved pharmacokinetics as compared with the small molecular weight drugs or the polymeric delivery systems with physically encapsulated drugs. Herein, a new type of oxidation-responsive polymer-drug conjugates composed of a poly(ethylene glycol) (PEG) block and a hydrophobic polyacrylate block to which Naproxen is attached through a phenylboronic ester linker is reported. The amphiphilic block copolymers are synthesized through the reversible addition-fragmentation chain transfer polymerization of the Naproxen-containing acrylic monomer using a PEG chain transfer agent. In neutral aqueous buffer, the conjugates formed nanoparticles with diameters of ≈150-300 nm depending on the length of the hydrophobic segment. The dynamic covalent bond of the phenylboronic ester is stabilized due to the hydrophobic microenvironment inside the nanoparticles. Upon exposure to H2 O2 , the phenylboronic ester is oxidized rapidly into the phenol derivative which underwent a 1,6-elimination reaction, releasing the intact Naproxen. The rate of drug release is influenced by the concentration of H2 O2 and the hydrophobic block length. This type of oxidation-responsive polymer-drug conjugate is feasible for other drugs containing hydroxyl group or amino group.

Acid-Sensitive Polypseudorotaxanes Based on Ortho Ester-Modified Cyclodextrin and Pluronic F-127.

We demonstrate a new type of acid-sensitive amphiphilic polypseudorotaxanes (PPRs) formed via inclusion complexation between Pluronic F127 and the hydrophobic ß-cyclodextrin (CD) derivative in alcoholic solvents. The 6-OH ortho ester-substituted hydrophobic ß-CD derivative (EMD-CD) was prepared by "click" reaction of ß-CD with 2-ethylidene-4-methyl-1,3-dioxalane under mild conditions. The water-insoluble EMD-CD (host) is capable of forming PPRs with F127 (guest) in ethanol or methanol but not in water, which is confirmed by 1H NMR, wide-angle X-ray diffraction, small-angle X-ray scattering, and the time-dependent threading kinetics. Depending on the host/guest ratio, the PPRs self-assembled into sheet-like structure or vesicular nanoparticles with different sizes in water. These PPR assemblies were stable at pH 8.4 but quickly dissociated into biocompatible products in neutral or in acidic buffers due to the hydrolysis of the ortho ester groups. Good biocompatibility, ease of fabrication, and extremely pH-sensitive character make the PPRs promising carriers for anticancer drug delivery. Moreover, the present work provides an alternative method for the preparation of PPRs composed of water-insoluble CD derivatives.

Oxidation-Promoted Degradation of Aliphatic Poly(carbonate)s via Sequential 1,6-Elimination and Intramolecular Cyclization.

We report a new type of oxidation-promoted fast-degradable aliphatic poly(carbonate)s (PCs) prepared by the ring-opening polymerization (ROP) of a six-membered cyclic carbonate containing a phenylboronic pinacol ester. The ROP of this monomer catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) proceeded rapidly at ambient temperature with a good control over molecular weight and polydispersity at high monomer conversion. The H2O2-induced decomposition of this cyclic monomer and its noncyclic carbonate analogue was first studied by 1H NMR in order to clearly demonstrate the degradation mechanism of the PCs. The results of 1H NMR, GPC, and Nile Red fluorescence measurements revealed that the PC nanoparticles formulated by the o/w emulsion method were stable in neutral buffer, but upon triggering with H2O2, they underwent rapid surface degradation via the consecutive processes of oxidation, 1,6-elimination, release of CO2, and intramolecular cyclization. The degradation rates of the nanoparticles were dependent on the concentration of H2O2, and the nanoparticles were even sensitive to 0.5 mM of H2O2.

Shell-sheddable, pH-sensitive supramolecular nanoparticles based on ortho ester-modified cyclodextrin and adamantyl PEG.

We report a new type of pH-sensitive supramolecular aggregates which possess a programmable character of sequential dePEGylation and degradation. As a platform of designing and building multifunctional supramolecular nanoparticles, a family of 6-OH ortho ester-modified ß-cyclodextrin (ß-CD) derivatives have been synthesized via the facile reaction between ß-CD and cyclic ketene acetals with different alkyl lengths. These asymmetric acid-labile ß-CD derivatives formed amphiphilic supramolecules with adamantane-modified PEG through host-guest interaction in polar solvents such as ethanol. The supramolecules can self-assemble in water to form acid-labile supramolecular aggregates. The results of TEM and light scattering measurements demonstrate that the size and morphology of the aggregates are influenced by the alkyl or PEG length and the host-guest feed ratio. By carefully balancing the alkyl and PEG lengths and adjusting the host-guest ratio, well-dispersed vesicles (50-100 nm) or sphere-like nanoparticles (200-500 nm) were obtained. Zeta potential measurements reveal that these supramolecular aggregates are capable of being surface-functionalized via dynamic host-guest interaction. The supramolecular aggregates were stable at pH 8.4 for at least 12 h as proven by the (1)H NMR and LLS measurements. However, rapid dePEGylation occurred at pH 7.4 due to the hydrolysis of the ortho ester linkages locating at the interface, which resulted in aggregation of the dePEGylated hydrophobic inner cores. Upon further decreasing the pH to 6.4, the hydrophobic cores were further degraded due to the acid-accelerated hydrolysis of the ortho esters. The incubation stability of the acid-labile supramolecular aggregates in neutral buffer could be improved by incorporating hydrophobic poly(ε-caprolactone) into the core of the aggregates.

Glucose-responsive hydrogels based on dynamic covalent chemistry and inclusion complexation.

A novel glucose-responsive hydrogel system based on dynamic covalent chemistry and inclusion complexation was described. Hydrogels are formed by simply mixing the solutions of three components: poly(ethylene oxide)-b-poly vinyl alcohol (PEO-b-PVA) diblock polymer, α-cyclodextrin (α-CD) and phenylboronic acid (PBA)-terminated PEO crosslinker. Dynamic covalent bonds between PVA and PBA provide sugar-responsive crosslinking, and the inclusion complexation between PEO and α-CD can promote hydrogel formation and enhance hydrogel stability. The ratios of the three components have a remarkable effect on the gelation time and the mechanical properties of the final gels. In rheological measurements, the hydrogels are demonstrated to possess solid-like behaviour and good structural recovery ability after yielding. The sugar-responsiveness of the hydrogels was examined by protein loading and release experiments, and the results indicate that this property is also dependent on the compositions of the gels; at a proper component ratio, a new glucose-responsive hydrogel system operating at physiological pH can be obtained. The combination of good biocompatibility of the three components and the easy preparation of hydrogels with tunable glucose-responsiveness may enable an alternative design of hydrogel systems that finds potential applications in biomedical and pharmaceutical fields, such as treatment of diabetes.