Synthesis and Self-Assembly of Thermoresponsive Biohybrid Graft Copolymers Based on a Combination of Passerini Multicomponent Reaction and Molecular Recognition.

Amphiphilic graft copolymers exhibit fascinating self-assembly behaviors. Their molecular architectures significantly affect the morphology and functionality of the self-assemblies. Considering the potential application of amphiphilic graft copolymers in the fabrication of nanocarriers, it is essential to synthesize well-defined graft copolymers with desired functional groups. Herein, the Passerini reaction and molecular recognition are introduced to the synthesis of functional thermoresponsive graft copolymers. A bifunctional monomer 2-((adamantan-1-yl)amino)-1-(4-((2-bromo-2-methylpropanoyl)oxy)phenyl)-2-oxoethyl methacrylate (ABMA) with a bromo group for atom transfer radical polymerization (ATRP) and an adamantyl group for molecular recognition is synthesized through the Passerini reaction. The graft copolymers are prepared by reversible addition-fragmentation transfer (RAFT) copolymerization of ABMA and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) followed by RAFT end group removal and ATRP of di(ethylene glycol)methyl ether methacrylate (DEGMA) initiated by the ABMA units. The graft copolymer P(OEGMA-co-ABMA)-g-PDEGMA can be functionalized with ß-cyclodextrin modified peptides, affording a thermoresponsive biohybrid graft copolymer. At a temperature above its lower critical solution temperature, the biohybrid graft copolymer self-assembles into peptide-modified polymersomes.

Dual-Prodrug-Based Hyaluronic Acid Nanoplatform Provides Cascade-Boosted Drug Delivery for Oxidative Stress-Enhanced Chemotherapy.

Insufficient drug accumulation in tumors severely limits the antitumor efficiency of hyaluronic acid (HA) nanomedicine in solid tumors due to superficial penetration depth, low cell uptake, and nonspecific drug release. Hence, we constructed a dual NO prodrug (alkynyl-JSK) and doxorubicin prodrug (cis-DOX)-conjugated HA nanoparticle (HA-DOX-JSK NPs), which achieved cascade-boosted drug delivery efficiency based on a relay strategy of NO-mediated deep tumor penetration─HA target CD44 tumor cell uptake─tumor microenvironment (TME)-responsive drug release. The nanoparticle demonstrated sustained and locoregionally GSH/GST-triggered NO release and GSH/pH-responsive DOX release in the tumor. The released NO first mediated collagen degradation, causing deep tumor penetration of nanoparticles in the dense extracellular matrix. Immediately, HA was relayed to enhance CD44-targeted tumor cell uptake, and then, the nanoparticles were finally triggered by specific TME to release DOX and NO in the deep tumor. Relying on the relayed delivery strategy, a significant improvement of DOX accumulation in tumors was realized. Moreover, NO depleted GSH-induced intracellular reactive oxygen species, enhancing DOX chemotherapy. Based on this strategy, the tumor inhibition rate in breast cancer was up to 87.8% in vivo. The relay drug-delivery HA system would greatly cascade-boost drug accumulation in deep tumors for efficient solid tumor therapy.

Versatile Hydrogel Dressing with Skin Adaptiveness and Mild Photothermal Antibacterial Activity for Methicillin-Resistant Staphylococcus Aureus-Infected Dynamic Wound Healing.

Bacterial infection often induces chronic repair of wound healing owing to aggravated inflammation. Hydrogel dressing exhibiting intrinsic antibacterial activity may substantially reduce the use of antibiotics for infected wound management. Hence, a versatile hydrogel dressing (rGB/QCS/PDA-PAM) exhibiting skin adaptiveness on dynamic wounds and  mild photothermal antibacterial activity is developed for safe and efficient infected wound treatment. Phenylboronic acid-functionalized graphene (rGB) and oxadiazole-decorated quaternary carboxymethyl chitosan (QCS) are incorporated into a polydopamine-polyacrylamide (PDA-PAM) network with multiple covalent and noncovalent bonds, which conferred the hydrogel with flexible mechanical properties, strong tissue adhesion and excellent self-healing ability on the dynamic wounds. Moreover, the glycocalyx-mimicking phenylboronic acid on the surface of rGB enables the hydrogel to specifically capture bacteria. The enhanced membrane permeability of QCS enhanced bacterial vulnerability to photothermal therapy（PTT）, which is demonstrated by efficient mild PTT antibacteria against methicillin-resistant Staphylococcus aureus in vitro and in vivo at temperatures of <49.6 °C. Consequently, the hydrogel demonstrate accelerated tissue regeneration on MRSA-infected wound in vivo, with an intact epidermis, abundant collagen deposition and prominent angiogenesis. Therefore, rGB/QCS/PDA-PAM is a versatile hydrogel dressing exhibiting inherent antibacterial activity and has considerable potential in treating wounds infected with drug-resistant bacteria.

Cascaded amplification of intracellular oxidative stress and reversion of multidrug resistance by nitric oxide prodrug based-supramolecular hydrogel for synergistic cancer chemotherapy.

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Facile Approach to Prepare rGO@Fe3O4 Microspheres for the Magnetically Targeted and NIR-responsive Chemo-photothermal Combination Therapy.

Near-infrared (NIR)-light responsive graphene have been shown exciting effect on cancer photothermal ablation therapy. Herein, we report on the preparation of Fe3O4-decorated hollow graphene microspheres (rGO@Fe3O4) by a facile spray drying and coprecipitation method for the magnetically targeted and NIR-responsive chemo-photothermal combination therapy. The microspheres displayed very high specific surface area (~ 120.7 m2 g-1) and large pore volume (~ 1.012 cm3 g-1), demonstrating distinct advantages for a high loading capacity of DOX (~ 18.43%). NIR triggered photothermal effect of the rGO@Fe3O4 microspheres responded in an on-off manner and induced a high photothermal conversion efficiency. Moreover, The Fe3O4 on the microspheres exhibited an excellent tumor cells targeting ability. The chemo-photothermal treatment based on rGO@Fe3O4/DOX showed superior cytotoxicity towards Hela cells in vitro. Our studies indicated that rGO@Fe3O4/DOX microcapsules have great potential in combined chemo-photothermal cancer treatment.

Mussel-Inspired General Interface Modification Method and Its Application in Polymer Reinforcement and as a Flame Retardant.

Inspired by the remarkable adhesion of mussels, the mimicking of natural adhesive molecules has been widely used for surface modification. In the present study, an economical and easily available biomimic material named as tannic acid-Fe3+ (TA-Fe3+) was first directly used as a surface modifier, carbonization agent, smoke inhibitor, and flame-retardant synergist. Compared with the flame-retardant magnesium hydroxide (Mg(OH)2), TA-Fe3+-modified Mg(OH)2 endowed polyamide 6 (PA 6) with improved mechanical performance and flame-retardant properties. The flame-retardant and smoke-suppressant properties were tested by the limiting oxygen index and cone calorimeter tests. The flame-retardation mechanism was investigated by thermogravimetric analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy. The tensile strength could increase up to 90%, and the modified flame retardant was found to have higher UL-94 grade with the same dosage of flame-retardant additives. The peak heat release rate, total heat release, peak of smoke production rate, and total smoke production were significantly reduced. The synergistic effect between TA-Fe3+ and Mg(OH)2 was also discussed. This study provides new insights into the direct utilization of a biomimicking adhesive molecule, TA-Fe3+, to realize simultaneous composite reinforcement and flame-retardant property enhancement. Meanwhile, because of the extensive synergies of flame-retardant metal oxide with iron element and the universal growth characteristics of TA-Fe3+, it has potential applications in the preparation of various flame-retardant polymers.