Engineering Entomopathogenic Fungi Using Thermal-Responsive Polymer to Boost Their Resilience against Abiotic Stresses.

Entomopathogenic fungi offer an ecologically sustainable and highly effective alternative to chemical pesticides for managing plant pests. However, the efficacy of mycoinsecticides in pest control suffers from environmental abiotic stresses, such as solar UV radiation and temperature fluctuations, which seriously hinder their practical application in the field. Herein, we discovered that the synthetic amphiphilic thermal-responsive polymers are able to significantly enhance the resistance of Metarhizium robertsii conidia against thermal and UV irradiation stresses. The thermosensitive polymers with extremely low cytotoxicity and good biocompatibility can be engineered onto the M. robertsii conidia surface by anchoring hydrophobic alkyl chains. Further investigations revealed that polymer supplementation remarkably augmented the capacity for penetration and the virulence of M. robertsii under heat and UV stresses. Notably, broad-spectrum entomopathogenic fungi can be protected by the polymers. The molecular mechanism was elucidated through exploring RNA sequencing and in vivo/vitro enzyme activity assays. This work provides a novel avenue for fortifying the resilience of entomopathogenic fungi, potentially advancing their practical application as biopesticides.

Responsive nanocellulose-PNIPAM millicapsules.

HYPOTHESIS: Milli- and micro-capsules are developed to facilitate the controlled release of diverse active ingredients by passive diffusion or a triggered burst. As applications expand, capsules are required to be increasingly multi-functional, combining benefits like encapsulation, response, release, and even movement. Balancing the increasingly complex demands of capsules is a desire to minimize material usage, requiring efficient structural and chemical design. Designing multifunctional capsules with complex deformation should be possible even after minimizing the material usage through use of sparse fiber networks if the fibers are coated with responsive polymers. EXPERIMENTS: Here capsules are created with a shell made from a mesh of nanoscale bacterial cellulose fibers that provide mechanical strength at very low mass levels, while a coating of thermoresponsive Poly(N-isopropylacrylamide), PNIPAM, on the fibers provides control of permeability, elastic response, and temperature response. These properties are varied by grafting different amounts of polymer using particular reaction conditions. FINDINGS: The addition of PNIPAM to the cellulose mesh capsule enhances its mechanical properties, enabling it to undergo large deformations and recover once stress is removed. The increased elastic response of the capsule also provides reinforcement against drying-induced capillary stresses, limiting the degree of shrinkage during dehydration. Time-lapse microscopy demonstrates thermoreversible swelling of the capsules in response to temperature change. Cycles of swelling and shrinkage drive solvent convection to and from the capsule interior, allowing exchange of contents and mixing with the bulk fluid on a time scale of seconds. Because the cellulose capsules are produced via emulsion-templated fermentation, the polymer-modified biocapsule concept introduced here presents a pathway toward the sustainable and scalable manufacture of multifunctional responsive capsules.

Fiber complex-stabilized high-internal-phase emulsion for allicin encapsulation: microstructure, stability, and thermal-responsive properties.

BACKGROUND: Stimuli-responsive emulsions have garnered significant attention for their ability to enhance sensory qualities and control the release of encapsulated nutrient in emulsion-based products. However, the characteristics of synthetic materials of fabricating stimuli-responsive emulsions have been a crucial limitation in the food industry. Regulating the behavior of molecules at the interface could potentially achieve the desired stimuli-responsive behavior, but currently there is limited information available. RESULTS: High-internal-phase emulsions (HIPEs) were fabricated for the encapsulation of allicin, stabilized by a complex of 20 g kg-1 whey protein amyloid fibrils (WPF) and 20 g kg-1 glycyrrhizin fibers (GA). The intermolecular interactions between WPF and GA in the fiber complexes were predominantly governed by hydrophobic and electrostatic forces. These complexes adsorbed and stacked around the oil droplets, forming a protective interfacial film that enhanced droplet stability. An increased proportion of WPF (WPF = 3:1 or 4:1) surrounding the oil droplets enhanced the accelerated storage stability of HIPEs, with instability indexes approaching 0.2. Additionally, HIPEs displayed a temperature-dependent modulus, with the emulsion stabilized by a WPF ratio of 3:1 showing the highest modulus at 85 °C. The encapsulation efficiency of allicin in HIPEs ranged from 88.69 ± 6.62% to 101 ± 1.37% at 25 °C, and from 31.95 ± 1.92% to 78.69 ± 4.63% after incubation at 85 °C for 8 h. The release profile of allicin from the HIPEs exhibited thermal responsiveness, depending on the interfacial content of GA. CONCLUSION: These findings indicated that the thermal-responsive properties of HIPEs can be strategically engineered by manipulating their interfacial characteristics. © 2024 Society of Chemical Industry.

Material Compatibility in 4D Printing: Identifying the Optimal Combination for Programmable Multi-Material Structures.

This study identifies the optimal combination of active and passive thermoplastic materials for producing multi-material programmable 3D structures. These structures can undergo shape changes with varying radii of curvature over time when exposed to hot water. The research focuses on examining the thermal, thermomechanical, and mechanical properties of active (PLA) and passive (PRO-PLA, ABS, and TPU) materials. It also includes the experimental determination of the radius of curvature of the programmed 3D structures. The pairing of active PLA with passive PRO-PLA was found to be the most effective for creating complex programmable 3D structures capable of two-sided transformation. This efficacy is attributed to the adequate apparent shear strength, significant differences in thermomechanical shrinkage between the two materials, identical printing parameters for both materials, and the lowest bending storage modulus of PRO-PLA among the passive materials within the activation temperature range. Multi-material 3D printing has also proven to be a suitable method for producing programmable 3D structures for practical applications such as phone stands, phone cases, door hangers, etc. It facilitates the programming of the active material and ensures the dimensional stability of the passive components of programmable 3D structures during thermal activation.

Thermal-responsive ß-cyclodextrin-based magnetic hydrogel as a de novo nanomedicine for chemo/hyperthermia treatment of cancerous cells.

A novel thermal-responsive ß-cyclodextrin-based magnetic hydrogel [ß-cyclodextrin-graft-poly(N-isopropylacrylamide)/Fe3O4 (ß-CD-g-PNIPAAm/Fe3O4)] was fabricated as a novel nanomedicine for chemo/hyperthermia treatment of cancer cells. Firstly, ß-CD was modified by maleic anhydride (MA) followed by copolymerization with NIPAAm monomer and thiol-end capped Fe3O4 nanoparticles (NPs) in the presence of a crosslinker through acrylamide-thiol polymerization system to afford a magnetic hydrogel. The saturation magnetization (δ s) value for developed hydrogel was determined to be 8.2 emu g-1. The hydrogel was physically loaded with an anticancer agent, doxorubicin hydrochloride (Dox). The encapsulation efficiency (EE) of drug into the hydrogel was obtained as 73 %. The system represented acceptable thermal-triggered drug release behavior that best fitted with Higuchi model, demonstrating the release of drug is mostly controlled by diffusion mechanism. The anticancer performance of the ß-CD-g-PNIPAAm/Fe3O4-Dox was evaluated using MCF7 cells by MTT-assay. In addition, flow cytometry analyses showed considerable cellular uptake of Dox in the cells treated with ß-CD-g-PNIPAAm/Fe3O4-Dox (∼70 %) compared to free Dox (∼28 %). As results, in time period of 48 h by combination of chemo- and hyperthermia-therapies, the developed system displayed greater anticancer efficiency than the free Dox.

Cellulose nanocrystal thermal smart molecular brushes with upper critical aggregation temperature.

Grafting thermo-responsive polymers onto cellulose nanocrystals (CNCs) and achieving critical temperature regulation has drawn significant research interest. The thermal transition behavior of CNCs can be controlled by adjusting the polymer molecular brushes on the CNCs surface. We synthesized poly((2-dimethylamino) ethyl methacrylate) (PDMAEMA) grafted CNCs via surface-initiated reversible addition-fragmentation chain transfer, followed by modifying PDMAEMA brushes into poly-3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (PDMAPS) brushes via quaternization. The critical temperature was regulated by modifying and grafting of poly (ethylene glycol) methacrylate. Found the thermal stimulus-responsive type and transition point of CNCs can be controlled by adjusting the surface molecular brushes. Ultraviolet-visible spectroscopy and dynamic light scattering analyses indicated that CNC-PDMAEMA aggregated above 70 °C, whereas CNC-PDMAPS aggregated below 31 °C. The thermo-responsive materials based on CNCs exhibited a conversion from a lower critical aggregation temperature to an upper critical aggregation temperature (UCAT) type. CNC-PDMAPS-mPEG was obtained by modifying and grafting for UCAT to be regulated to approximately 37 °C, which is close to the human body temperature. CNC-PDMAPS and CNC-PDMAPS-mPEG exhibited only microscopic alterations and could encapsulate and release substances. Therefore, they demonstrate considerable potential for biomedical applications.

Laser-activable murine ferritin nanocage for chemo-photothermal therapy of colorectal cancer.

Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.

Novel pH- and thermal-responsive oleogel capsules: Featuring an oleogel core and ultrathin calcium-alginate shell.

Oleogels have been explored as a new lipid-based delivery system, however, their insolubility and unsuitable shape severely limit their application in food systems. Herein, core-shell oleogel capsules with high monodispersity (coefficient variation (CV) < 5%)) were prepared via gravity-assisted co-flowing microfluidic device and simply air-drying. The oleogel capsules with oleogel core and ultrathin calcium-alginate shell were prepared. Oleogel capsules maintained their original shape at pH = 2.0 but swelled rapidly at pH = 6.8 and 7.4. The swelling ratio of shell can be adjusted by inner fluid flow rate (Qin). Notably, the core with beeswax (BW) crystal network, effectively improved the stability performances and also could provide thermal response. Finally, the oleogel capsules demonstrated excellent sustained release and UV protection of lipophilic bioactives. This work sheds light on development of novel oleogel capsules, making them ideal candidates for smart food encapsulation applications.

Thermal-Responsive Gel-Based Overheat Limiter Enabled Intelligent Photothermal Therapy.

Uncontrolled and excessive photothermal heating in photothermal therapy (PTT) inevitably causes thermal damage to surrounding normal tissues, severely limiting the universality and safety of PTT. To address this issue, an intelligent cooling thermal-responsive (ICTR) gel containing poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-AM))microgel is applied onto the skin to realize intelligent PTT, which can avoid excessive heating and accidental injury. The high near-infrared (NIR) light transmittance (> 95%) of the ICTR gel ensures effective light delivery at low temperatures, while the refractive index of the P(NIPAM-AM) microgel increases remarkably when the temperature exceeds a predetermined threshold, resulting in progressively enhanced light scattering and weakened photothermal conversion. In animal studies, the negative feedback regulation of ICTR gel on light transmittance and photothermal heating allows the photothermal temperature in the lesion site to be stabilized within the effective therapeutic range (45 °C) while ensuring that the skin surface temperature does not exceed 35 °C. Compared with the severe skin thermal damage found in the histological staining of mice skin receiving conventional PTT, the mice skin receiving the ICTR gel-enabled intelligent PTT remains in good condition. This study establishes an intelligent and universal paradigm for PTT thermal regulation, which is of great significance for achieving safe and effective PTT.

Body temperature responsive capsules templated from Pickering emulsion for thermally triggered release of ß-carotene.

In recent years, functional foods with lipophilic nutraceutical ingredients are gaining more and more attention because of its potential healthy and commercial value, and developing of various bioderived food-grade particles for use in fabrication of Pickering emulsion has attracted great attentions. Herein, the bio-originated sodium caseinate-lysozyme (Cas-Lyz) complex particles were firstly designed to be used as a novel interfacial emulsifier for Pickering emulsions. Pickering emulsions of various food oils were all successfully stabilized by the Cas-Lyz particles without addition of any synthetic surfactants, while the fluorescence microscopy and SEM characterizations clearly evidenced Cas-Lyz particles were attached on the surface of emulsion droplets. Additionally, the Cas-Lyz particles stabilized emulsion can also be used to encapsulate the ß-carotene-loaded soybean oil, suggestion a potential method to carry lipophilic bioactive ingredients in an aqueous formulation for food, cosmetic and medical industry. At last, we present a Pickering emulsion strategy that utilizes biocompatible, edible and body temperature-responsive lard oil as the core material in microcapsules, which can achieve hermetic sealing and physiological temperature-triggered release of model nutraceutical ingredient (ß-carotene).

Thermally and Photothermally Triggered Cytocompatible Triple-Shape-Memory Polymer Based on a Graphene Oxide-Containing Poly(ε-caprolactone) and Acrylate Composite.

Triple-shape-memory polymers (triple-SMPs) are a class of polymers capable of fixing two temporary shapes and recovering sequentially from the first temporary shape to the second temporary shape and, last, to the permanent shape. To accomplish a sequential shape change, a triple-SMP must have two separate shape-fixing mechanisms triggerable by distinct stimuli. Despite the biomedical potential of triple-SMPs, a triple-SMP that with cells present can undergo two different shape changes via two distinct cytocompatible triggers has not previously been demonstrated. Here, we report the design and characterization of a cytocompatible triple-SMP material that responds separately to thermal and light triggers to undergo two distinct shape changes under cytocompatible conditions. Tandem triggering was achieved via a photothermally triggered component, comprising poly(ε-caprolactone) (PCL) fibers with graphene oxide (GO) particles physically attached, embedded in a thermally triggered component, comprising a tert-butyl acrylate-butyl acrylate (tBA-BA) matrix. The material was characterized in terms of thermal properties, surface morphology, shape-memory performance, and cytocompatibility during shape change. Collectively, the results demonstrate cytocompatible triple-shape behavior with a relatively larger thermal shape change (an average of 20.4 ± 4.2% strain recovered for all PCL-containing groups) followed by a smaller photothermal shape change (an average of 3.5 ± 0.8% strain recovered for all PCL-GO-containing groups; samples without GO showed no recovery) with greater than 95% cell viability on the triple-SMP materials, establishing the feasibility of triple-shape memory to be incorporated into biomedical devices and strategies.

Self-Destructive Structural Color Liquids for Time-Temperature Indicating.

Vaccines are undoubtedly a powerful weapon in our fight against global pandemics, as demonstrated in the recent COVID-19 case, yet they often face significant challenges in reliable cold chain transport. Despite extensive efforts to monitor their time-temperature history, current time-temperature indicators (TTIs) suffer from limited reliability and stability, such as difficulty in avoiding human intervention, inapplicable to subzero temperatures, narrow tracking temperature ranges, or susceptibility to photobleaching. Herein, we develop a class of structural color materials that harnesses dual merits of fluidic nature and structural color, enabling thermal-triggered visible color destruction based on triggering agent-diffusion-induced irreversible disassembly of liquid colloidal photonic crystals for indicating the time-temperature history of the cold chain transport. These self-destructive structural color liquids (SCLs) exhibit inherent irreversibility, superior sensitivity, tunable self-destructive time (minutes to days), and a wide tracking temperature range (-70 to +37 °C). Such self-destructive SCLs can be conveniently packaged into flexible TTIs for monitoring the storage and exposure status of diverse vaccines via naked-eye inspection or mobile phone scanning. By overcoming the shortcomings inherent in conventional TTIs and responsive photonic crystals, these self-destructive SCLs can increase their compatibility with cold chain transport and hold promise for the development and application of the next-generation intelligent TTIs and photonic crystals.

A Thermal-Responsive Zwitterionic Polymer Gel as a Filtrate Reducer for Water-Based Drilling Fluids.

It is crucial to address the performance deterioration of water-based drilling fluids (WDFs) in situations of excessive salinity and high temperature while extracting deep oil and gas deposits. The focus of research in the area of drilling fluid has always been on filter reducers that are temperature and salt resistant. In this study, a copolymer gel (PAND) was synthesized using acrylamide, N-isopropyl acrylamide, and 3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate through free-radical polymerization. The copolymer gel was then studied using FTIR, NMR, TGA, and element analysis. The PAND solution demonstrated temperature and salt stimulus response characteristics on rheology because of the hydrophobic association effect of temperature-sensitive monomers and the anti-polyelectrolyte action of zwitterionic monomers. Even in conditions with high temperatures (180 °C) and high salinities (30 wt% NaCl solution), the water-based drilling fluid with 1 wt% PAND displayed exceptional rheological and filtration properties. Zeta potential and scanning electron microscopy (SEM) were used to investigate the mechanism of filtration reduction. The results indicated that PAND could enhance bentonite particle colloidal stability, prevent bentonite particle aggregation, and form a compact mud cake, all of which are crucial for reducing the filtration volume of water-based drilling fluid. The PAND exhibit excellent potential for application in deep and ultra-deep drilling engineering, and this research may offer new thoughts on the use of zwitterionic polymer gel in the development of smart water-based drilling fluid.

Thermal-Responsive Hydrogel Actuators with Photo-Programmable Shapes and Actuating Trajectories.

Thermal-responsive hydrogel actuators have aroused a wide scope of research interest and have been extensively studied. However, their actuating behaviors are usually monotonous due to their unchangeable shapes and structures. Here, we report thermal-responsive poly(isopropylacrylamide-co-2-(dimethylamino)ethyl methacrylate)/alginate hydrogels with programmable external shapes and internal actuating trajectories. The volume phase transition temperatures of the resulting hydrogels can be tuned in a wide temperature range from 32 to above 50 °C by adjusting the monomer composition. While the formation and photo-dissociation of Fe3+-carboxylate tri-coordinates within the entire hydrogel network enable photo-responsive shape memory property, the insufficient dissociation of the tri-coordinates along the irradiation path gives rise to gradient crosslinking for realizing thermal-responsive actuation. Controlling the evolution of the gradient structure facilitates the regulation of the actuating amplitude. Furthermore, we show that the combination of these two types of shape-changing functionalities leads to more flexible and intricate shape-changing behaviors. One interesting application, a programmable hook with changeable actuating behaviors for lifting different objects with specific shapes, is also demonstrated. The proposed strategy can be extended to other types of actuating hydrogels with more advanced actuating behaviors.

A Metal Ion and Thermal-Responsive Bilayer Hydrogel Actuator Achieved by the Asymmetric Osmotic Flow of Water between Two Layers under Stimuli.

Shape-morphing hydrogels have drawn great attention due to their wide applications as soft actuators, while asymmetric responsive shape-morphing behavior upon encountering external stimuli is fundamental for the development of hydrogel actuators. Therefore, in this work, bilayer hydrogels were prepared and the shrinkage ratios (LA/LN) of the AAm/AAc layer to the NIPAM layer immersed in different metal ion solutions, leading to bending in different directions, were investigated. The difference in the shrinkage ratio was attributed to the synergistic effect of the osmolarity difference between the inside and outside of the hydrogels and the interaction difference between the ion and hydrogel polymer chains. Additionally, under thermal stimuli, the hydrogel actuator would bend toward the NIPAM layer due to the shrinkage of the hydrogel networks caused by the hydrophilic-hydrophobic phase transition of NIPAM blocks above the LCST. This indicates that metal ion and thermal-responsive shape-morphing hydrogel actuators with good mechanical properties could be used as metal ion or temperature-controllable switches or other smart devices.

Grafting Hollow Covalent Organic Framework Nanoparticles with Thermal-Responsive Polymers for the Controlled Release of Preservatives.

Covalent organic frameworks (COFs) hold great potential in various applications because of their well-defined pore structures and morphologies. However, most COF materials demonstrate poor dispersibility in solvents that significantly limits their processing and applications. Herein, we report the synthesis of COF-based hollow nanoparticles (h-NPs) with good water dispersibility, high capacity, and thermal responsiveness to load essential oil molecules for longer-term preservation of fruits. Imine-based COF h-NPs possessing a pore width of 1.3 nm, inner/outer diameters of ∼150/239 nm, and high crystallinity were synthesized and grafted with water-soluble polymers such as polyethylene glycol or poly(N-isopropylacrylamide) (PNIPAM) with molecular weights of 1-3 kDa. The h-NP products with grafting densities of 0.6-2.1 nm-2 can be well dispersed in water at room temperature. PNIPAM-grafted ones are temperature-responsive in that they can precipitate out from the dispersion at 40 °C and redisperse at 25 °C for at least 15 cycles. The h-NPs are used as nanocarriers to load essential oils such as hexanal and trans-2-hexenal with a high capacity of 1.1 g/g for fruit fresh-keeping, and the encapsulated preservatives can be released controllably at 25-40 °C as regulated by the grafted polymers. As a result, the storage time of cherry tomatoes can be prolonged by 4 days compared to the control run. Moreover, these h-NPs can be recycled and reused. Our work highlights the potential of COF nanomaterials grafting with stimuli-responsive polymers for controlled release application in various food preservation.

Bio-Mimetic Actuators of a Photothermal-Responsive Vitrimer Liquid Crystal Elastomer with Robust, Self-Healing, Shape Memory, and Reconfigurable Properties.

Soft actuators with apparent uniqueness in exhibiting complex shape morphing are highly desirable for artificial intelligence applications. However, for the majority of soft actuators, in general, it is challenging to achieve versatility, durability, and configurability simultaneously. Enormous works are devoted to meet the multifunctional smart actuators, to little effect. Herein, self-healing and bio-mimetic smart actuators are proposed based on azobenzene chromophores and dynamic disulfide bonds. Benefiting from the dynamic and drivable vitrimer liquid crystal elastomer (V-LCE) materials, a series of actuators with single or compound dynamic three-dimensional structures were fabricated, which were capable of double-stimuli response and complex "bionic" motions, such as the blooming of a flower, grasping and loosening an object, and so forth. Moreover, these flexible actuators showed fascinating properties, such as high robustness, excellent elasticity-plasticity shape-memory properties (Rf and Rr are close to 100%), easily reconfigurable property, and self-healing. This smart V-LCE provides a guideline to design and fabricate soft versatility actuators, which has prospects for developing smart bionic and artificial intelligence devices.

Thermal-Responsive and Fire-Resistant Materials for High-Safety Lithium-Ion Batteries.

As one of the most efficient electrochemical energy storage devices, the energy density of lithium-ion batteries (LIBs) has been extensively improved in the past several decades. However, with increased energy density, the safety risk of LIBs becomes higher too. The frequently occurred battery accidents worldwide remind us that safeness is a crucial requirement for LIBs, especially in environments with high safety concerns like airplanes and military platforms. It is generally recognized that the catastrophic thermal runaway (TR) event is the major cause of LIBs related accidents. Tremendous efforts have been devoted to coping with the TR concerns in LIBs, and thus enhance battery safety. This review first gives an introduction to the fundamentals of LIBs and the origins of safety issues. Then, the authors summarize the recent advances to improve the safety of LIBs with a unique focus on thermal-responsive and fire-resistant materials. Finally, a perspective is proposed to guide future research directions in this field. It is anticipated this review will stimulate inspiration and arouse extensive studies on further improvement in battery safety.

Gold nanorods-mediated efficient synergistic immunotherapy for detection and inhibition of postoperative tumor recurrence.

Tumor recurrence after surgery is the main cause of treatment failure. However, the initial stage of recurrence is not easy to detect, and it is difficult to cure in the late stage. In order to improve the life quality of postoperative patients, an efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. In this paper, two kinds of theranostic agents based on gold nanorods (AuNRs) platform were prepared. AuNRs and quantum dots (QDs) in one agent was used for the detection of carcinoembryonic antigen (CEA), using fluorescence resonance energy transfer (FRET) technology to indicate the occurrence of in situ recurrence, while AuNRs in the other agent was used for photothermal therapy (PTT), together with anti-PDL1 mediated immunotherapy to alleviate the process of tumor metastasis. A series of assays indicated that this synergistic immunotherapy could induce tumor cell death and the increased generation of CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Besides, more immune factors (IL-2, IL-6, and IFN-γ) produced by synergistic immunotherapy were secreted than mono-immunotherapy. This cooperative immunotherapy strategy could be utilized for diagnosis and treatment of postoperative tumor recurrence at the same time, providing a new perspective for basic and clinical research.

NIR-triggered thermo-responsive biodegradable hydrogel with combination of photothermal and thermodynamic therapy for hypoxic tumor.

Hypoxia is a typical feature of solid tumors, which highly limits the application of the oxygen-dependent therapy. Also, the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor. Thereby, we designed a novel localized injectable hydrogel combining the photothermal therapy (PTT) and the thermodynamic therapy (TDT), which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy. In our study, gold nanorods (AuNRs) and 2,2'-Azobis[2-(2-imidazalin-2-yl)propane] dihydrochlaride (AIPH) were incorporated into the hydrogel networks, which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide (NIPAM) and hydrophilic glycidyl methacrylate modified hyaluronic acid (HA-GMA) to fabricate an injectable and near-infrared (NIR) responsive hydrogel. The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation, but also generate free radicals even in hypoxic condition. Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors, achieving the controlled drug release on demand. The designed hydrogel with a sufficient loading capacity, excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation. The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen. Therefore, this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical.