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Bilirubin (BR) is among the most potent endogenous antioxidants that originates from the heme catabolic pathway. Despite being considered as a dangerous and cytotoxic waste product at high concentrations, BR has potent antioxidant effects leading to the reduction of oxidative stress and inflammation, which play an important role in the development and progression of cancer. The purpose of this study is to introduce PEGylated BR nanoparticles (NPs), themselves or in combination with other anti-cancer agents. BR is effective when loaded into various nanoparticles and used in cancer therapy. Interestingly, BRNPs can be manipulated to create stimuli-responsive carriers providing a sustained and controlled, as well as on-demand, release of drug in response to internal or external factors such as reactive oxygen species, glutathione, light, enzymes, and acidic pH. This review suggests that BRNPs have the potential as tumor microenvironment-responsive delivery systems for effective targeting of various types of cancers., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Addressing the challenge of poor wound healing in chronic wounds remains complex, as the underlying physiological mechanisms are still not fully understood. Traditional wound dressings often fail to meet the specific needs of the chronic wound healing process. Recently, considerable interest has shifted toward employing biomacromolecule-based smart wound dressings to facilitate wound healing. These stimuli-responsive dressings have undergone substantial development to manage local drug delivery, demonstrating promising therapeutic effects in treating chronic wound defects. They have displayed improved drug release profiles both in vitro and in vivo. Recently, there have been advancements in the development of innovative dual and multi-stimuli responsive dressings that react to combinations of signals including pH-temperature, pH-enzyme, pH-ROS, pH-glucose, pH-NIR, and multiple stimuli. This paper offers an in-depth review of recent progress in responsive wound dressings based on biomacromolecules, with a specific focus on their design, drug release capabilities, and therapeutic advantages., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteoarthritis (OA) is the most prevalent chronic joint disorder and is a major cause of disability among the elderly population. The degeneration and damage of articular cartilage associated with OA can result in a diminished range of motion in joints, subsequently impacting fundamental activities such as ambulation, standing, and grasping objects. In severe cases, it may culminate in disability. Traditional pharmacological treatments are often accompanied by various side effects, while invasive surgical procedures increase the risk of infection and thrombosis. Consequently, identifying alternative new methods for OA treatment remains a formidable challenge. With advancements in responsive hydrogel drug delivery platforms, an increasing number of strategies have emerged to enhance OA treatment protocols. Injectable response hydrogel drug delivery platforms show many advantages in treating OA, including improved biocompatibility, prolonged drug release duration, elevated drug loading capacity and enhanced sensitivity. This article reviews the recent progress of injectable responsive hydrogel drug delivery platform for OA treatment over the past few years. These innovative methodologies present new strategies and directions for future OA treatment while summarizing a series of challenges faced during the clinical transformation of injectable response hydrogel drug delivery platforms. Overall, injectable responsive hydrogel drug delivery platforms show great potential in treating OA, especially regarding improving drug retention time and stimulus-responsive release at the lesion sites. These innovative methods provide new hope for future OA treatment and point the way for clinical applications.

Four-dimensional printing refers to a process through which a 3D printed object transforms from one structure into another through the influence of an external energy input. Self-folding structures have been extensively studied to advance 3D printing technology into 4D using stimuli-responsive polymers. Designing and applying self-folding structures requires an understanding of the material properties so that the structural designs can be tailored to the targeted applications. Poly(N-iso-propylacrylamide) (PNIPAM) was used as the thermo-responsive material in this study to 3D print hydrogel samples that can bend or fold with temperature changes. A double-layer printed structure, with PNIPAM as the self-folding layer and polyethylene glycol (PEG) as the supporting layer, provided the mechanical robustness and overall flexibility to accommodate geometric changes. The mechanical properties of the multi-material 3D printing were tested to confirm the contribution of the PEG support to the double-layer system. The desired folding of the structures, as a response to temperature changes, was obtained by adding kirigami-inspired cuts to the design. An excellent shape-shifting capability was obtained by tuning the design. The experimental observations were supported by COMSOL Multiphysics ® software simulations, predicting the control over the folding of the double-layer systems.

Spinal cord injury (SCI) is a debilitating condition that can result in significant functional impairment and loss of quality of life. There is a growing interest in developing new therapies for SCI, and hydrogel-based multimodal therapeutic strategies have emerged as a promising approach. They offer several advantages for SCI repair, including biocompatibility, tunable mechanical properties, low immunogenicity, and the ability to deliver therapeutic agents. This article provides an overview of the recent advances in hydrogel-based therapy strategies for SCI repair, particularly within the past three years. We summarize the SCI hydrogels with varied characteristics such as phase-change hydrogels, self-healing hydrogel, oriented fibers hydrogel, and self-assembled microspheres hydrogel, as well as different functional hydrogels such as conductive hydrogels, stimuli-responsive hydrogels, adhesive hydrogel, antioxidant hydrogel, sustained-release hydrogel, etc. The composition, preparation, and therapeutic effect of these hydrogels are briefly discussed and comprehensively evaluated. In the end, the future development of hydrogels in SCI repair is prospected to inspire more researchers to invest in this promising field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In cancer therapy, it is essential to selectively release cytotoxic agents into the tumor to prevent the adverse effects associated with anticancer drugs. Thus, in this study, a stimuli-sensitive polymer-drug conjugate was synthesized for selective drug release. Doxorubicin (DOX) and docetaxel (DTX) were conjugated onto novel poly(jasmine lactone) based copolymer via a thioketal (TK) linker. In addition, a photosensitizer (chlorin e6) was attached to the polymer, which served as a reactive oxygen species generator to cleave the TK linker. The conjugate is readily self-assembled into micelles less than 100 nm in size. Micelles demonstrate a notable increase in their ability to cause cell death when exposed to near-infrared (NIR) light on MDA-MB-231 breast cancer cells. The increase in cytotoxicity is higher than that observed with the combination of free DOX and DTX. The accumulation of DOX in the nucleus after release from the micelles (laser irradiation) was also confirmed by confocal microscopy. In the absence of light, micelles did not show any toxicity while the free drugs were found toxic irrespective of the light exposure. The obtained results suggest the targeted drug delivery potential of micelles regulated by the external stimuli, i.e., NIR light.

The design of novel drug delivery systems is exceptionally critical in disease treatments. Among the existing drug delivery systems, mesoporous silica nanoparticles (MSNs) have shown profuse promise owing to their structural stability, tunable morphologies/sizes, and ability to load different payload chemistry. Significantly, the presence of surface silanol groups enables functionalization with relevant drugs, imaging, and targeting agents, promoting their utility and popularity among researchers. Stimuli-responsive silanol conjugates have been developed as a novel, more effective way to conjugate, deliver, and release therapeutic drugs on demand and precisely to the selected location. Therefore, it is urgent to summarize the current understanding and the surface silanols' role in making MSN a versatile drug delivery platform. This review provides an analytical understanding of the surface silanols, chemistry, identification methods, and their property-performance correlation. The chemistry involved in converting surface silanols to a stimuli-responsive silica delivery system by endogenous/exogenous stimuli, including pH, redox potential, temperature, and hypoxia, is discussed in depth. Different chemistries for converting surface silanols to stimuli-responsive bonds are discussed in the context of drug delivery. The critical discussion is culminated by outlining the challenges in identifying silanols' role and overcoming the limitations in synthesizing stimuli-responsive mesoporous silica-based drug delivery systems., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

Ionic liquids (ILs) play a crucial role in the design of novel materials. The ionic nature of ILs provides numerous advantages in drug delivery, acting as a green solvent or active ingredient to enhance the solubility, permeability, and binding efficiency of drugs. They could also function as a structuring agent in the development of nano/micro particles for drug delivery, including micelles, vesicles, gels, emulsion, and more. This review summarize the ILs and IL-based gel structures with their advanced drug delivery applications. The first part of review focuses on the role of ILs in drug formulation and the applications of ILs in drug delivery. The second part of review offers a comprehensive overview of recent drug delivery applications of IL-based gel. It aims to offer new perspectives and attract more attention to open up new avenues in the biomedical applications of ILs and IL-based gels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To design and evaluate a matrix metalloproteinase 9 (MMP-9)-responsive hydrogel for vital pulp therapy., Methods: A peptide linker with optimized sensitivity toward MMP-9 was crosslinked with 4-arm poly (ethylene glycol)-norbornene (PEG-NB) by thiol-norbornene photo-polymerization. This resulted in the formation of a hydrogel network in which the peptide IDR-1002 was incorporated. Hydrogel characterization and gelation kinetics were examined with Fourier-transform infrared spectroscopy, scanning electron microscopy, rheological testing, and swelling evaluation. Hydrogel degradation was examined through multiple exposure to pre-activated MMP-9, to simulate flare-ups of dental pulp inflammation. The IDR-1002 released from degraded hydrogels was measured with high-performance liquid chromatography. Effect of IDR-1002 released from hydrogels on one-week-old multispecies oral biofilms was evaluated using confocal laser scanning microscopy., Results: MMP-9-responsive, injectable, and photo-crosslinkable hydrogels were successfully synthesized. When hydrogel degradation and release of IDR-1002 were examined with exposure to pre-activated MMP-9, IDR-1002 release was significantly correlated with elevated levels of MMP-9 (p < 0.05). The effectiveness of IDR-1002 in killing bacteria in multispecies oral biofilms was significantly enhanced when the hydrogels were immersed in 10 nM or 20 nM pre-activated MMP-9, compared to immersion in phosphate-buffered saline (p < 0.05)., Conclusions: The MMP-9-responsive hydrogel is a promising candidate for on-demand delivery of bioactive agent in vital pulp therapy., Clinical Significance: MMP-9 is one of the most important diagnostic and prognostic biomarkers for pulpitis. An MMP-9-responsive hydrogel has potential to be used as an in-situ on-demand release system for the diagnosis and treatment of dental pulp inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Nanotechnology-enabled pesticide delivery systems have been widely studied and show great prospects in modern agriculture. Nanodelivery systems not only achieve the controlled release of agrochemicals but also possess many unique characteristics. This study presents the development of a pH-responsive pesticide nanoformulation utilizing hollow mesoporous silica nanoparticles (HMSNs) as a nanocarrier. The nanocarrier was loaded with the photosensitive pesticide prochloraz (Pro) and then combined with ZnO quantum dots (ZnO QDs) through electrostatic interactions. ZnO QDs serve as both the pH-responsive gatekeeper and the enhancer of the pesticide. The results demonstrate that the prepared nanopesticide exhibits high loading efficiency (24.96%) for Pro. Compared with Pro technical, the degradation rate of Pro loaded in HMSNs@Pro@ZnO QDs was reduced by 26.4% after 24 h ultraviolet (UV) exposure, indicating clearly improved photostability. In a weak acidic environment (pH 5.0), the accumulated release of the nanopesticide after 48 h was 2.67-fold higher than that in a neutral environment. This indicates the excellent pH-responsive characteristic of the nanopesticide. The tracking experiments revealed that HMSNs can be absorbed by rice leaves and subsequently transported to other tissues, indicating their potential for effective systemic distribution and targeted delivery. Furthermore, the bioactivity assays confirmed the fungicidal efficacy of the nanopesticide against rice blast disease. Therefore, the constructed nanopesticide holds great prospect in nanoenabled agriculture, offering a novel strategy to enhance pesticide utilization.

The chemotherapeutic drug of doxorubicin (DOX) has witnessed widespread applications for treating various cancers. DOX-treated dying cells bear cellular modifications which allow enhanced presentation of tumor antigen and neighboring dendritic cell activation. Furthermore, DOX also facilitate the immune-mediated clearance of tumor cells. However, disadvantages such as severe off-target toxicity, and prominent hydrophobicity have resulted in unsatisfactory clinical therapeutic outcomes. The effective delivery of DOX drug molecules is still challenging despite the rapid advances in nanotechnology and biomaterials. Huge progress has been witnessed in DOX nanoprodrugs owing to their brilliant benefits such as tumor stimuli-responsive drug release capacity, high drug loading efficiency and so on. This review summarized recent progresses of DOX prodrug-based nanomedicines to provide deep insights into future development and inspire researchers to explore DOX nanoprodrugs with real clinical applications., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akbar, Khattak, Khan, Saddozai, Ali, AlAsmari, Zaheer and Badar.)

Glutathione (GSH) consumption-enhanced cancer therapies represent important potential cancer treatment strategies. Herein, we developed a new multifunctional diselenide-crosslinked hydrogel with glutathione peroxidase (GPx)-like catalytic activity for GSH depletion-enhanced glucose oxidase (GOx)-mediated tumor starvation and hypoxia-activated chemotherapy. By increasing acid and H 2 O 2 during GOx-induced tumor starvation, the degradation of the multiresponsive scaffold could be promoted, which led to accelerated release of the loaded drugs. Meanwhile, the overproduced H 2 O 2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H 2 O 2 and subsequent multimodal cancer treatment. Following the GOx-induced amplification of hypoxia, tirapazamine (TPZ) was transformed into the highly toxic benzotriazinyl radical (BTZ·), exhibiting enhanced antitumor activity. This GSH depletion-augmented cancer treatment strategy effectively boosted GOx-mediated tumor starvation and activated the hypoxia drug, leading to significantly enhanced local anticancer efficacy. STATEMENT OF SIGNIFICANCE: There has been a growing interest in depleting intracellular GSH as a potential strategy for improving ROS-based cancer therapy. Herein, a bioresponsive diselenide-functionalized dextran-based hydrogel with GPx-like catalytic activity was developed for GSH consumption-enhanced local starvation- and hypoxia-activated melanoma therapy. Results showed that the overproduced H 2 O 2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H 2 O 2 and subsequent multimodal cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Stimuli-responsive or smart materials have recently shown a significant impact on the frontier of material science and engineering. The exponential development of synthetic host molecules (SHMs) over the last decades and their corresponding host-guest chemistry, have empowered researchers with new opportunities to design and construct tailored or guest-specific smart materials. In this Minireview, we present the recent advancements in synthetic host based smart materials, ranging from the fabrication strategies to the state-of-art applications including adsorption, separation, luminescence, self-healing and actuation. The role that the host-guest chemistry plays in these systems is highlighted throughout to give a better prospective of the available possibilities for emerging materials of future economies., (© 2023 Wiley-VCH GmbH.)

Sustainable and precise fortification practices are necessary to ensure food security for the increasing human population. Precision agriculture aims to minimize the use of fertilizers and pesticides by developing smart materials for real-life agricultural practices. Here, we show that biomimetic mineralization can be efficiently employed to encapsulate and controllably release plant biostimulants (MiZax-3) to improve the quality and yield of capsicum ( Capsicum annum ) crops in field experiments. ZIF-8 encapsulation of MiZax-3 (MiZIFs) could significantly enhance its stability up to around 679 times (6p value = 0.0072) at field conditions. Our results demonstrate that the coordinating Zn ions and the MiZax-3 play a vital role in improving Zn content in the produced fruits by 2-fold, which is the first report of this nature on Zn content in fruits. We envision this platform as a starting point to investigate other biocompatible coordination-based platforms for micronutrient delivery in precision agriculture.

Metal-Organic Frameworks (MOFs) have emerged as a promising biomedical material due to its unique features such as high surface area, pore volume, variable pore size, flexible functional groups, and excellent efficiency for drug loading. In this review, we explored the use of novel and smart metal organic frameworks as drug delivery vehicles to discover a safer and more controlled mode of drug release aiming to minimize their side effects. Here, we systematically discussed the background of MOFs following a thorough review on structural and physical properties of MOFs, their synthesis techniques, and the important characteristics to establish a strong foundation for future research. Furthermore, the current status on the potential applications of MOF-based stimuli-responsive drug delivery systems, including pH-, ion-, temperature-, light-, and multiple responsive systems for the delivery of anticancer drugs has also been presented. Lastly, we discuss the prospects and challenges in implementation of MOF-based materials in the drug delivery. Therefore, this review will help researchers working in the relevant fields to enhance their understanding of MOFs for encapsulation of various drugs as well as their stimuli responsive mechanism., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Stimuli-responsive synthetic polypeptide-containing block copolymers have received considerable attention in recent years. Especially, unique thermo-induced sol-gel phase transitions were observed for elaborately-designed amphiphilic diblock copolypeptides and a range of poly(ethylene glycol) (PEG)-polypeptide block copolymers. The thermo-induced gelation mechanisms involve the evolution of secondary conformation, enhanced intramolecular interactions, as well as reduced hydration and increased chain entanglement of PEG blocks. The physical parameters, including polymer concentrations, sol-gel transition temperatures and storage moduli, were investigated. The polypeptide hydrogels exhibited good biocompatibility in vitro and in vivo , and displayed biodegradation periods ranging from 1 to 5 weeks. The unique thermo-induced sol-gel phase transitions offer the feasibility of minimal-invasive injection of the precursor aqueous solutions into body, followed by in situ hydrogel formation driven by physiological temperature. These advantages make polypeptide hydrogels interesting candidates for diverse biomedical applications, especially as injectable scaffolds for 3D cell culture and tissue regeneration as well as depots for local drug delivery. This review focuses on recent advances in the design and preparation of injectable, thermo-induced physically crosslinked polypeptide hydrogels. The influence of composition, secondary structure and chirality of polypeptide segments on the physical properties and biodegradation of the hydrogels are emphasized. Moreover, the studies on biomedical applications of the hydrogels are intensively discussed. Finally, the major challenges in the further development of polypeptide hydrogels for practical applications are proposed., (© The Author(s) 2023. Published by Oxford University Press.)

Deoxyribonucleic acid (DNA) hydrogels are a unique class of programmable, biocompatible materials able to respond to complex stimuli, making them valuable in drug delivery, analyte detection, cell growth, and shape-memory materials. However, unmodified DNA hydrogels in the literature are very soft, rarely reaching a storage modulus of 10 3  Pa, and they lack functionality, limiting their applications. Here, a DNA/small-molecule motif to create stiff hydrogels from unmodified DNA, reaching 10 5  Pa in storage modulus is used. The motif consists of an interaction between polyadenine and cyanuric acid-which has 3-thymine like faces-into multimicrometer supramolecular fibers. The mechanical properties of these hydrogels are readily tuned, they are self-healing and thixotropic. They integrate a high density of small, nontoxic molecules, and are functionalized simply by varying the molecule sidechain. They respond to three independent stimuli, including a small molecule stimulus. These stimuli are used to integrate and release DNA wireframe and DNA origami nanostructures within the hydrogel. The hydrogel is applied as an injectable delivery vector, releasing an antisense oligonucleotide in cells, and increasing its gene silencing efficacy. This work provides tunable, stimuli-responsive, exceptionally stiff all-DNA hydrogels from simple sequences, extending these materials' capabilities., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The complexity of the tumor microenvironment (TME) severely hinders the therapeutic effects of various cancer treatment modalities. The TME differs from normal tissues owing to the presence of hypoxia, low pH, and immune-suppressive characteristics. Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors. Recently, polymeric nanomedicines have been widely used in cancer therapy, because their synthesis can be controlled and they are highly modifiable, and have demonstrated great potential to remodel the TME. In this review, we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME, aiming to provide insights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy., Competing Interests: Competing interests: All authors declare that they have contributed to the manuscript and have no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Sepsis is a life-threatening disease caused by the dis-functioning of the immune response to pathogenic infections. Despite, the discovery of modern therapeutics and treatments of sepsis are lacking due to the resistance of pathogens. Metronidazole is an antibiotic commonly used to treat bacterial infections, but usage is limited and challenging by a short half-life period. In this research work, fabricate a pH-responsive drug delivery system for controlled release of metronidazole targeted molecules. We exemplified that, the encapsulation of hydrophilic metronidazole drug within a hydrophobic ZIF-90 framework can be enhanced the pH-responsive drug release under acidic conditions. The ZIF-90 frameworks only decompose in under acidic solutions, they are highly stable in physiological conditions. The pH-responsive protonation mechanism of ZIF-90 frameworks promotes the quick release of metronidazole within cells. The antimicrobial proficiency of zinc and metronidazole will expose a synergistic effect in ROS-mediated bacterial inhibition and auto-immunity boosting of normal cells. In vitro, antibacterial activity results revealed that the MI@ZIF-90 nano drug delivery system effectively eradicated human infectious pathogens at the lowest concentrations. In anti-fungal activity, studies show excellent growth inhibition against human pathogenic fungi Aspergillus fumigatus and Candida albicans. Finally, the PBMC cytocompatibility study concludes, that the fabricated MI@ZIF-90 drug delivery system is non-toxic to biomedical applications. The overall research findings highlight the design of a smart drug delivery system for sepsis treatment. In future it will be an efficient, low-cost, and biocompatible pharmaceutics for pediatric sepsis management processes., Competing Interests: Declaration of competing interest On behalf of the authors declared that there is no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Herein, we report a stimuli-responsive hydrogel with inhibitory activity against Escherichia coli prepared by chemical crosslinking of carboxymethyl chitosan (CMCs) and hydroxyethyl cellulose (HEC). The hydrogels were prepared by esterification of chitosan (Cs) with monochloroacetic acid to produce CMCs which were then chemically crosslinked to HEC using citric acid as the crosslinking agent. To impart a stimuli responsiveness property to the hydrogels, polydiacetylene-zinc oxide (PDA-ZnO) nanosheets were synthesized in situ during the crosslinking reaction followed by photopolymerization of the resultant composite. To achieve this, ZnO was anchored on carboxylic groups in 10,12-pentacosadiynoic acid (PCDA) layers to restrict the movement of the alkyl portion of PCDA during crosslinking CMCs and HEC hydrogels. This was followed by irradiating the composite with UV radiation to photopolymerize the PCDA to PDA within the hydrogel matrix so as to impart thermal and pH responsiveness to the hydrogel. From the results obtained, the prepared hydrogel had a pH-dependent swelling capacity as it absorbed more water in acidic media as compared to basic media. The incorporation of PDA-ZnO resulted in a thermochromic composite responsive to pH evidenced by a visible colour transition from pale purple to pale pink. Upon swelling, PDA-ZnO-CMCs-HEC hydrogels had significant inhibitory activity against E. coli attributed to the slow release of the ZnO nanoparticles as compared to CMCs-HEC hydrogels. In conclusion, the developed hydrogel was found to have stimuli-responsive properties and inhibitory activity against E. coli attributed to zinc nanoparticles.

Multi stimuli-responsive aggregation-induced emission (AIE) active polymers have great application prospects in high-tech innovations. Herein, three types of tetraphenylethylene (TPE)-containing monomers were synthesized and utilized in preparing TPE-appended maleic anhydride terpolymers. After hydrolysis, the produced TPE-appended maleic acid terpolymers have identical linear charge densities but different "primary" structures, which created widely varied microenvironments around the carboxylate and TPE groups. Benefiting from the synergistic interaction of the TPE moiety and the terpolymer conformation change, the TPE-appended maleic acid terpolymers exhibited fluorescence changes in response to multi stimuli, including pH, ionic strength, Ca 2+ , and bovine serum albumin. On both the "signaling" and the "stimuli acceptor" sides, the multi stimuli-responsive fluorescence behavior was influenced markedly by the terpolymer primary structure. The fundamental insights gained in the present work are important for developing an efficient and versatile stimuli-responsive AIE-active polymer platform for chemo-sensing, bioimaging, and so on.

Cesium lead halide perovskite quantum dots (QDs) have attracted immense attention for luminescent materials due to their narrow emission bands and color-tunable emission. However, indispensable surface ligands originating from ligand-assisted synthesis strategies severely deteriorate the stability and luminescence properties of QDs since these ligands have a highly dynamic binding. Herein, we used a green fluorescence BODIPY molecule containing thiol (named SH-BDP) to regulate the CsPbBr 3 QDs surface by ligand regulation. Density functional theory calculations proved that the SH-BDP molecule could bind to the exposed Pb of CsPbBr 3 QDs stronger than traditional ligands to form stable SH-BDP-QDs. Moreover, the SH-BDP fixed on the CsPbBr 3 QDs surface can improve water and light resistance. It also served as a knob to tune their luminescence properties and the reversible thermal-stimuli response. Finally, the multi-response property of SH-BDP-QDs was realized under polar solvent or heat along with UV light. In addition, we used the SH-BDP-QDs to create various anti-counterfeiting labels; several luminous modes were achieved under different external stimuli, which improved the quality of the optical anti-counterfeiting labels and ensured information security. This work indicates the immense potential of surface ligand manipulation in improving the stability and multi-stimuli-responsive optical encoding of perovskite quantum dots., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This work demonstrates thermally programmable dynamic capillarity in exclusively engineered nanochannels functionalized by grafted smart elastomeric layers onto their inner surfaces. Tunable control of the capillarity is observed over the temperature window of 25-31 °C, deciphering the possibility of a sevenfold alteration in the rate of capillary flow. A simple theory explains the confluence of viscous and capillary interactions as mediated by the non-trivial interplay of the substrate wettability, confinement-induced surface layering of molecules, and thermally activated modulation of surface tension, to bring out this intriguing effect. The technology is demonstrated to be completely reconfigurable over the intended spatial and temporal regimes, via selective grafting of the channel surface and preferential choice of the activation temperature. Such favorable features as opposed to more complex yet non-reconfigurable flow manipulation strategies previously reported are likely to open up new possibilities of highly precise controlled nanofluidic manipulation of temperature-sensitive biological samples and chemical species on-demand, for applications ranging from biomedical technologies to energy harvesting and water purification., (© 2022 Wiley-VCH GmbH.)

Electromerism is a very well-known phenomenon in transition metal chemistry. In main group chemistry, this concept has only started getting attention recently. We report stimuli responsive low-valent silicon compounds exhibiting electromerism. A mixed-valent silaiminyl-silylene 1, [LSi-Si(NDipp)L] (L=PhC(N t Bu) 2 ), was synthesized in a single step from amidinate-chlorosilylene. Compound 1 has two interconnected Si atoms in formally +I and +III oxidation states. Upon treatment with Lewis acidic Cu I X (X=mesityl, Cl, Br, I), electron redistribution occurs resulting in the formation of [{LSi(NDipp)Si(L)}-CuX], in which both silicon atoms are in the +II formal oxidation state. Removal of the copper center from [{LSi(NDipp)Si(L)}-CuX] by using a Lewis basic carbene led to reformation of the precursor [LSi-Si(NDipp)L]. Thus, the process is fully reversible. This showcases the first example of Lewis acid/base-induced reversible electromerism in silicon chemistry., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Intelligent nanomedicines integrated with stimuli-responsive components enable on-demand customizable treatment options which would improve therapeutic outcome and reduce systemic toxicity. In this work, we explore the synergistic therapeutic potential of photodynamic therapy and immunometabolic modulation to achieve tumour regression and to trigger an adaptive immunity to prevent tumour recurrence. The therapeutic potential of the fabricated Bioengineered Immunomodulatory Organelle targeted Nanozymes (BIONs) was tested on 3D printed mini-brains which could effectively recapitulate the biologically relevant interactions between glioblastoma cells and macrophages. In the presence of glioblastoma organotypic brain slices, activated BIONs upregulated the cell surface expression of CD86, a costimulatory molecule and CD83, maturation marker, on monocyte derived dendritic cells, suggesting its ability to elicit a strong immune response. Furthermore, the antigen pulsed dendritic cells by chemotaxis and transendothelial migration readily relocate into the draining lymph node where they present the antigenic cargo to enable the proliferation of T lymphocytes. The stealth and tunable catalytic activity of BIONs prevent ROS mediated diseases such as acute kidney injury by providing environment dependent protection without compromising on its promising anti-cancer activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

As it is closely associated with tumor proliferation, metastasis, and the immunosuppressive microenvironment, the dysfunctional Hippo pathway has become an extremely attractive target for treating multiple cancers. However, to date, the corresponding chemotherapeutic nanomedicines have not been developed. Herein, a supramolecular self-delivery nanomedicine with in situ transforming capacity was tailor-constructed for Hippo-pathway restoration, and its inhibitory effect against tumor growth and metastasis was investigated in a highly aggressive triple-negative breast cancer (TNBC) model. Stimulated by overexpressed glutathione (GSH) and esterase in cancer cells, the self-assembled nanomedicine transformed from inactive nanospheres to active nanofibers conjugating tyrosvaline and spatiotemporally synchronously released the covalently linked flufenamic acid in situ , together activating the maladjusted Hippo pathway by simultaneously acting on different targets upstream and downstream. The transcriptional expression of Yes-associated protein (YAP) and related growth-promoted genes were significantly reduced, finally significantly repressing the proliferation and metastasis of cancer cells. Additionally, the Hippo-pathway restoration showed an excellent radiosensitization effect, making the targeted therapy combined with radiotherapy display a prominent synergistic in vivo anticancer effect against TNBC. This work reports a specifically designed smart nanomedicine to restore the function of the Hippo pathway and sensitize radiotherapy, providing an attractive paradigm for targeted drug delivery and cancer combination therapy.

Cancer seriously threatens human health. Surgery, radiotherapy and chemotherapy are the three pillars of traditional cancer treatment, with targeted therapy and immunotherapy emerging over recent decades. Standard drug regimens are mostly executed via intravenous injection (IV), especially for chemotherapy agents. However, these treatments pose severe risks, including off-target toxic side effects, low drug accumulation and penetration at the tumor site, repeated administration, etc., leading to inadequate treatment and failure to meet patients' needs. Arising from these challenges, a local regional anticancer strategy has been proposed to enhance therapeutic efficacy and concomitantly reduce systemic toxicity. With the advances in biomaterials and our understanding of the tumor microenvironment, in situ stimulus-responsive hydrogels, also called smart hydrogels, have been extensively investigated for local anticancer therapy due to their injectability, compatibility and responsiveness to various stimuli (pH, enzyme, heat, light, magnetic fields, electric fields etc.). Herein, we focus on the latest progress regarding various stimuli that cause phase transition and drug release from smart hydrogels in local regional anticancer therapy. Additionally, the challenges and future trends of the reviewed in situ smart hydrogels for local drug delivery are summarized and proposed.

Systemic treatments for rheumatoid arthritis are associated with many side effects. This study aimed to minimize the side effects associated with the systemic administration of leflunomide (LEF) by formulating LEF-loaded emulsomes (EMLs) for intra-articular administration. Additionally, EMLs were loaded with supramagnetic nanoparticles (SPIONs) to enhance joint localization, where a magnet was placed on the joint area after intra-articular administration. Full in vitro characterization, including colloidal characteristics, entrapment efficiency, and in vitro release were conducted besides the in vivo evaluation in rats with adjuvant-induced arthritis. In vivo study included joint diameter measurement, X-ray radiographic analysis, RT-PCR analysis, Western blotting, ELISA for inflammatory markers, and histopathological examination of dissected joints. The particle size and entrapment efficiency of the selected LEF SPION EMLs were 198.2 nm and 83.7%, respectively. The EMLs exhibited sustained release for 24 h. Moreover, in vivo evaluation revealed LEF SPION EMLs to be superior to the LEF suspension, likely due to the increase in LEF solubility by nanoencapsulation that improved the pharmacological effects and the use of SPION that ensured the localization of EMLs in the intra-articular cavity upon administration.

The design of new remediation strategies and materials for treating saline-alkaline soils is of fundamental and practical importantance for many applications. Conventional soil remediation strategies mainly focus on the development of fertilizers or additives for water, nutrient, and heavy metal managements in soils, but they often overlook a soil sensing function for early detection of salinization/alkalization levels toward optimal and timely soil remediation. Here, new smart soils, structurally consisting of the upper signal soil and the bottom hygroscopic bed and chemically including zwitterionic, thermo-responsive poly(NIPAM-co-VPES) and poly(NIPAM-co-SBAA) aerogels in each soil layer are formulated. Upon salinization, the resultant smart soils exhibit multiple superior capacities for reducing the soil salinity and alkalinity through ion exchange, controlling the water cycling, modulating the degradation of pyridine-base ligands into water-soluble, nitrogenous salts-rich ingredients for soil fertility, and real-time monitoring salinized soils via pH-induced allochroic color changes. Further studies of plant growth in smart soils with or without salinization treatments confirm a synergy effect of soil remediation and soil sensing on facilitating the growth of plants and increasing the saline-alkaline tolerance of plants. The esign concept of smart soils can be further expanded for soil remediation and assessment., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Over the last couple of decades, stimuli-responsive supramolecular gels comprising synthetic short peptides as building blocks have been explored for various biological and material applications. Though a wide range of stimuli has been tested depending on the structure of the peptides, light as a stimulus has attracted extensive attention due to its non-invasive, non-contaminant, and remotely controllable nature, precise spatial and temporal resolution, and wavelength tunability. The integration of molecular photo-switch and low-molecular-weight synthetic peptides may thus provide access to supramolecular self-assembled systems, notably supramolecular gels, which may be used to create dynamic, light-responsive "smart" materials with a variety of structures and functions. This short review summarizes the recent advancement in the area of light-sensitive peptide gelation. At first, a glimpse of commonly used molecular photo-switches is given, followed by a detailed description of their incorporation into peptide sequences to design light-responsive peptide gels and the mechanism of their action. Finally, the challenges and future perspectives for developing next-generation photo-responsive gels and materials are outlined.

In this work, using supramolecular polyurethanes theories, two polycaprolactone-based polyurethanes with 2-ureido-4-[1H]-pyrimidinone (UPy) motifs capable of forming quadruple hydrogen bonds were synthetized and characterized, focusing our attention on their capability to show thermally activated shape-memory response. In particular, 1 H NMR analyses confirmed the chemical structure of the supramolecular polyurethanes, while DSC showed their totally amorphous morphology. DMTA in tensile mode was used to study their thermally activated shape-memory properties. In our case, the UPy units are the switching domains while the network formed by the segregated hard segments is the permanent domain obtained materials with excellent shape-memory response at both 100 and 85 °C. These materials are promising for multi-responsive materials where bio-based and potentially recyclable polymers with excellent shape-memory properties are needed.

Traditional open surgery complications are typically due to trauma caused by accessing the procedural site rather than the procedure itself. Minimally invasive surgery allows for fewer complications as microdevices operate through small incisions or natural orifices. However, current minimally invasive tools typically have restricted maneuverability, accessibility, and positional control of microdevices. Thermomagnetic-responsive microgrippers are microscopic multi-fingered devices that respond to temperature changes due to the presence of thermal-responsive polymers. Polymeric devices, made of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) and polypropylene fumarate (PPF), self-fold due to swelling and contracting of the hydrogel layer. In comparison, soft metallic devices feature a pre-stressed metal bilayer and polymer hinges that soften with increased temperature. Both types of microdevices can self-actuate when exposed to the elevated temperature of a cancerous tumor region, allowing for direct targeting for biopsies. Microgrippers can also be doped to become magnetically responsive, allowing for direction without tethers and the retrieval of microdevices containing excised tissue. The smaller size of stimuli-responsive microgrippers allows for their movement through hard-to-reach areas within the body and the successful extraction of intact cells, RNA and DNA. This review discusses the mechanisms of thermal- and magnetic-responsive microdevices and recent advances in microgripper technology to improve minimally invasive surgical techniques.

Lung cancer is one of the most common cancers, affecting more than 2.1 million people across the globe every year. A very high occurrence and mortality rate of lung cancer have prompted active research in this area with both conventional and novel forms of therapies including the use of nanomaterials based drug delivery agents. Specifically, the unique physico-chemical and biological properties of porous nanomaterials have gained significant momentum as drug delivery agents for delivering a combination of drugs or merging diagnosis with targeted therapy for cancer treatment. This review focuses on the emergence of nano-porous materials for drug delivery in lung cancer. The review analyses the currently used nanoporous materials, including inorganic, organic and hybrid porous materials for delivering drugs for various types of therapies, including chemo, radio and phototherapy. It also analyses the selected research on stimuli-responsive nanoporous materials for drug delivery in lung cancer before summarizing the various findings and projecting the future of emerging trends. This review provides a strong foundation for the current status of the research on nanoporous materials, their limitations and the potential for improving their design to overcome the unique challenges of delivering drugs for the treatment of lung cancer., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

Protein therapeutics have become increasingly popular for the treatment of a variety of diseases owing to their specificity to targets of interest. However, challenges associated with them have limited their use for a range of ailments, including the limited options available for local controlled delivery. To address this challenge, degradable hydrogel microparticles, or microgels, loaded with model biocargoes were created with tunable release profiles or triggered burst release using chemistries responsive to endogenous or exogeneous stimuli, respectively. Specifically, microfluidic flow-focusing was utilized to form homogenous microgels with different spontaneous click chemistries that afforded degradation either in response to redox environments for sustained cargo release or light for on-demand cargo release. The resulting microgels were an appropriate size to remain localized within tissues upon injection and were easily passed through a needle relevant for injection, providing means for localized delivery. Release of a model biopolymer was observed over the course of several weeks for redox-responsive formulations or triggered for immediate release from the light-responsive formulation. Overall, we demonstrate the ability of microgels to be formulated with different materials chemistries to achieve various therapeutic release modalities, providing new tools for creation of more complex protein release profiles to improve therapeutic regimens.

Fluorescent materials presenting unique color changes in response to external stimuli have wide applications in information storage and anticounterfeiting. However, developing intelligent fluorescent materials with high security levels and dynamically displaying encrypted information is still a challenge. Herein, we report a new method for constructing excellent fluorescent materials by loading the photochromic molecule spiropyran into a lanthanide metal-organic framework. Controlling the isomerization of the spiropyran unit regulates the fluorescence resonance energy transfer (FRET) mechanism between the spiropyran acceptor and the lanthanide donor, leading to an exceptional reversible absorption/luminescence modulation ability. As the irradiation time is extended, the fluorescent color changes continuously from yellow-greenish to orange and then to red through the FRET process within 60 s. This composite system has great potential in anticounterfeiting because of the following advantages: (1) the materials have different fluorescence emissions and optical colors regulated by ultraviolet radiation, which is convenient for designing complex anticounterfeiting patterns; (2) the system can be repeatedly verified quickly and exhibit dynamic fluorescence color within 60 s, having great potential in advanced anticounterfeiting, where time is key in encryption/decryption. These unique advantages will greatly enhance the reliability of anticounterfeiting measures and increase the difficulty of anticounterfeiting.

The present study aimed to develop a stable interconnected matrix as a sustained release drug delivery material. Arabinoxylan (AX) was extracted from ispaghula husk and then crosslinked with different concentrations, i.e., 0.5, 1.0, and 1.5 g of CaCl 2 per 0.25 g of AX. The crosslinking was confirmed through Fourier transform infrared spectroscopy. The swelling capacity of crosslinked AX (CL-AX) was evaluated against buffer solutions of pH 1.2, 6.8, 7.4, and water. The swelling capacity increased from pH 1.2 to pH 7.4 and followed the second order swelling kinetics. The swelling study also revealed that CL-AX with 1.0 g CaCl 2 showed maximum swelling capacity. The swelling-deswelling (on-off switching) behavior of CL-AX was evaluated in water-ethanol, water-0.9% NaCl solution, and buffer solutions of pH 7.4-1.2 and showed responsive swelling-deswelling behavior. Scanning electron microscopy revealed a highly porous nature of CL-AX with a mesh of thin fibrous networking. Hemocompatibility studies of CL-AX revealed its non-thrombogenic and nonhemolytic attributes. The CL-AX matrix tablet prolonged the release of enalapril maleate for 24 h, and the drug release followed the zero order kinetics and super case-II transport mechanism. Therefore, CL-AX can be recognized as a stimuli responsive and hemocompatible biomaterial with sustained drug release potential.

Design and fabrication of freestanding chiro-photonic crystal film with the ability to change color over the whole visible light spectrum is appealing for anticounterfeiting technology and smart labels. Utilizing a newly synthesized light-responsive molecular motor functionalized with cholesterol (chol-MM) on the rotor, novel light-controlled photonic crystal is prepared by doping the novel chol-MM into liquid crystals (LCs). Thanks to the liquid crystalline cholesterol substituent, the chol-MM can be triggered by visible light (420 nm). At the same time, the miscibility of chol-MM in LC matrix is significantly enhanced. Integrating the chol-MM with thermochromic hydrogen-bonded LC matrix, thermal and light dual-responsive cholesteric LC (CLC) material is prepared, in which the nanoscale helical pitch is tunable by photo-induced molecular motions of chol-MM. More importantly, utilizing UV-initiated polymerization of the visible light-modulated CLC material, structural colored photonic crystal films with arbitrary colorful patterns are fabricated. Such freestanding helical nanostructured labels have potential in the application of encrypted communication and anticounterfeiting., (© 2022 Wiley-VCH GmbH.)

Architecting an appropriate platform for biomedical applications requires setting a balance between simplicity and complexity. Polysaccharides (PSAs) play essential roles in our life in food resources, structural materials, and energy storage capacitors. Moreover, the diversity and abundance of PSAs have made them an indispensable part of food ingredients and cosmetics. PSA-based hydrogels have been extensively reviewed in biomedical applications. These hydrogels can be designed in different forms to show optimum performance. For instance, electroactive PSA-based hydrogels respond under an electric stimulus. Such performance can be served in stimulus drug release and determining cell fate. This review classifies and discusses the structure, properties, and applications of the most important polysaccharide-based electroactive hydrogels (agarose, alginate, chitosan, cellulose, and dextran) in medicine, focusing on their usage in tissue engineering, flexible electronics, and drug delivery applications., (Copyright © 2021. Published by Elsevier Ltd.)

Capsules have hollow cores and closed wall structures, and they have attracted considerable interest due to their wide applications and significance in life science. The engineering process of bioinspired capsules and related applications have earned heavy concerns. However, the mechanism of capsule formation is often ignored. Herein, based on polyornithine (POR) and tannic acid (TA), two facile strategies to engineer bioinspired capsules were proposed, and the formation mechanisms were deeply explored. We found that the oxidized state of TA had a profound influence not on the thickness or permeability of the formed capsule but on the mechanism and generation process. Compared to TA/POR capsules produced from TA without oxidization (TA/POR), capsules produced from TA with preoxidization (oTA/POR) had thicker shells with higher impermeability. The dominant construction mode in the shells of TA/POR capsules was electrostatic interactions but became Schiff base bonds in oTA/POR capsules. The permeability of oTA/POR displayed pH reversibility and strong pH dependence, with 100% permeability at lower pH and 100% impermeability at pH 7, completing loading/releasing kinetics in minutes at pH 4. We believe these findings contribute to knowledge of bioinspired capsules from engineering processes and formation mechanisms, extending their applications in various fields, such as in drug delivery, artificial cells, and sensors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recently, we presented a strategy for packaging peptides as side-chains in high-density brush polymers. For this globular protein-like polymer (PLP) formulation, therapeutic peptides were shown to resist proteolytic degradation, enter cells efficiently and maintain biological function. In this paper, we establish the role charge plays in dictating the cellular uptake of these peptide formulations, finding that peptides with a net positive charge will enter cells when polymerized, while those formed from anionic or neutral peptides remain outside of cells. Given these findings, we explored whether cellular uptake could be selectively induced by a stimulus. In our design, a cationic peptide is appended to a sequence of charge-neutralizing anionic amino acids through stimuli-responsive cleavable linkers. As a proof-of-concept study, we tested this strategy with two different classes of stimuli, exogenous UV light and an enzyme (a matrix metalloproteinase) associated with the inflammatory response. The key finding is that these materials enter cells only when acted upon by the stimulus. This approach makes it possible to achieve delivery of the polymers, therapeutic peptides or an appended cargo into cells in response to an appropriate stimulus., (© 2021 Wiley-VCH GmbH.)

Synthetic cells, which mimic cellular function within a minimal compartment, are finding wide application, for instance in studying cellular communication and as delivery devices to living cells. However, to fully realise the potential of synthetic cells, control of their function is vital. An array of tools has already been developed to control the communication of synthetic cells to neighbouring synthetic cells or living cells. These tools use either chemical inputs, such as small molecules, or physical inputs, such as light. Here, we examine these current methods of controlling synthetic cell communication and consider alternative mechanisms for future use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Smith, Chowdhry and Booth.)

Biomedical luminescence imaging in the near-infrared (NIR, 700-1700 nm) region has shown great potential in visualizing biological processes and pathological conditions at cellular and animal levels, owing to the reduced tissue absorption and scattering compared to light in the visible (400-700 nm) region. To overcome the background interference and signal attenuation during intensity-based luminescence imaging, lifetime imaging has demonstrated a reliable imaging modality complementary to intensity measurement. Several selective or environment-responsive probes have been successfully developed for luminescence lifetime imaging and multiplex detection. This review summarizes recent advances in the application of luminescence lifetime imaging at cellular and animal levels in NIR-I and NIR-II regions. Finally, the challenges and further directions of luminescence lifetime imaging are also discussed., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Abstract: Bacterial biofilm infections have been threatening the human's life and health globally for a long time because they typically cause chronic and persistent infections. Traditional antibiotic therapies can hardly eradicate biofilms in many cases, as biofilms always form a robust fortress for pathogens inside, inhibiting the penetration of drugs. To address the issues, many novel drug carriers emerged as promising strategies for biofilm treatment. Among them, stimuli-responsive nanocarriers have attracted much attentions for their intriguing physicochemical properties, such as tunable size, shape and surface chemistry, especially smart drug release characteristic. Based on the microenvironmental difference between biofilm infection sites and normal tissue, many stimuli, such as bacterial products accumulating in biofilms (enzymes, glutathione, etc.), lower pH and higher H 2 O 2 levels, have been employed and proved in favor of "on-demand" drug release for biofilm elimination. Additionally, external stimuli including light, heat, microwave and magnetic fields are also able to control the drug releasing behavior artificially. In this review, we summarized recent advances in stimuli-responsive nanocarriers for combating biofilm infections, and mainly, focusing on the different stimuli that trigger the drug release., 摘要: , , 。 , , 。 , , 。 , -, , , , 。 , , (, ), pHH 2 O 2 , ""。 , , , , 。 , , 。., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Youke Publishing Co.,Ltd 2021.)

Smart materials represent an elegant class of (macro)-molecules endowed with the ability to react to chemical/physical changes in the environment. Herein, we prepared new photo responsive azobenzenes possessing halogen bond donor groups. The X-ray structures of two molecules highlight supramolecular organizations governed by unusual noncovalent bonds. In azo dye I-azo-NO 2 , the nitro group is engaged in orthogonal H···O···I halogen and hydrogen bonding, linking the units in parallel undulating chains. As far as compound I-azo-NH-MMA is concerned, a non-centrosymmetric pattern is formed due to a very rare I···π interaction involving the alkene group supplemented by hydrogen bonds. The Cambridge Structural Database contains only four structures showing the same I···CH 2 =C contact. For all compounds, an 19 F-NMR spectroscopic analysis confirms the formation of halogen bonds in solution through a recognition process with chloride anion, and the reversible photo-responsiveness is demonstrated upon exposing a solution to UV light irradiation. Finally, the intermediate I-azo-NH 2 also shows a pronounced color change due to pH variation. These azobenzenes are thereby attractive building blocks to design future multi-stimuli responsive materials for highly functional devices.

Peptide-based hydrogels have captivated remarkable attention in recent times and serve as an excellent platform for biomedical applications owing to the impressive amalgamation of unique properties such as biocompatibility, biodegradability, easily tunable hydrophilicity/hydrophobicity, modular incorporation of stimuli sensitivity and other functionalities, adjustable mechanical stiffness/rigidity and close mimicry to biological molecules. Putting all these on the same plate offers smart soft materials that can be used for tissue engineering, drug delivery, 3D bioprinting, wound healing to name a few. A plethora of work has been accomplished and a significant progress has been realized using these peptide-based platforms. However, designing hydrogelators with the desired functionalities and their self-assembled nanostructures is still highly serendipitous in nature and thus a roadmap providing guidelines toward designing and preparing these soft-materials and applying them for a desired goal is a pressing need of the hour. This review aims to provide a concise outline for that purpose and the design principles of peptide-based hydrogels along with their potential for biomedical applications are discussed with the help of selected recent reports., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Das and Das.)

Gas therapy has received widespread attention from the medical community as an emerging and promising therapeutic approach to cancer treatment. Among all gas molecules, nitric oxide (NO) was the first one to be applied in the biomedical field for its intriguing properties and unique anti-tumor mechanisms which have become a research hotspot in recent years. Despite the great progress of NO in cancer therapy, the non-specific distribution of NO in vivo and its side effects on normal tissue at high concentrations have impaired its clinical application. Therefore, it is important to develop facile NO-based nanomedicines to achieve the on-demand release of NO in tumor tissue while avoiding the leakage of NO in normal tissue, which could enhance therapeutic efficacy and reduce side effects at the same time. In recent years, numerous studies have reported the design and development of NO-based nanomedicines which were triggered by exogenous stimulus (light, ultrasound, X-ray) or tumor endogenous signals (glutathione, weak acid, glucose). In this review, we summarized the design principles and release behaviors of NO-based nanomedicines upon various stimuli and their applications in synergistic cancer therapy. We also discuss the anti-tumor mechanisms of NO-based nanomedicines in vivo for enhanced cancer therapy. Moreover, we discuss the existing challenges and further perspectives in this field in the aim of furthering its development.

Peptide-based drug delivery systems have many advantages when compared to synthetic systems in that they have better biocompatibility, biochemical and biophysical properties, lack of toxicity, controlled molecular weight via solid phase synthesis and purification. Lysosomes, solid lipid nanoparticles, dendrimers, polymeric micelles can be applied by intravenous administration, however they are of artificial nature and thus may induce side effects and possess lack of ability to penetrate the blood-brain barrier. An analysis of nontoxic drug delivery systems and an establishment of prospective trends in the development of drug delivery systems was needed. This review paper summarizes data, mainly from the past 5 years, devoted to the use of peptide-based carriers for delivery of various toxic drugs, mostly anticancer or drugs with limiting bioavailability. Peptide-based drug delivery platforms are utilized as peptide-drug conjugates, injectable biodegradable particles and depots for delivering small molecule pharmaceutical substances (500 Da) and therapeutic proteins. Controlled drug delivery systems that can effectively deliver anticancer and peptide-based drugs leading to accelerated recovery without significant side effects are discussed. Moreover, cell penetrating peptides and their molecular mechanisms as targeting peptides, as well as stimuli responsive (enzyme-responsive and pH-responsive) peptides and peptide-based self-assembly scaffolds are also reviewed.

Glioblastoma multiforme (GBM) is a grade IV malignant brain tumor with a median survival time of approximately 12-16 months. Because of its highly aggressive and heterogeneous nature it is very difficult to remove by surgical resection. Herein we have reported dual stimuli-responsive and biodegradable in situ hydrogels of oligosulfamethazine-grafted gelatin and loaded with anticancer drug paclitaxel (PTX) for preventing the progress of Glioblastoma. The oligosulfamethazine (OSM) introduced to the gelatin backbone for the formation of definite and stable in situ hydrogel. The hydrogels transformed from a sol to a gel state upon changes in stimuli. pH and temperature and retained a distinct shape after subcutaneous administration in BALB/c mice. The viscosity of the sol state hydrogels was tuned by varying the feed molar ratio between gelatin and OSM. The porosity of the hydrogels was confirmed to be lower in higher degree OSM by SEM. Sustained release of PTX from hydrogels in physiological environments (pH 7.4) was further retarded up to 63% in 9th days in tumor environments (pH 6.5). While the empty hydrogels were non-toxic in cultured cells, the hydrogels loaded with PTX showed antitumor efficacy in orthotopic-GBM xenograft mice. Collectively, the gelatin-OSM formed porous hydrogels and released the cargo in a sustained manner in tumor environments efficiently suppressing the progress of GBM. Thus, gelatin-OSM hydrogels are a potential candidate for the direct delivery of therapeutics to the local areas in brain diseases., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Microbial growth and fluctuations in environmental conditions have been shown to cause microbial contamination and deterioration of food. Thus, it is paramount to develop reliable strategies to effectively prevent the sale and consumption of contaminated or spoiled food. Responsive packaging systems are designed to react to specific stimuli in the food or environment, such as microorganisms or temperature, then implement an informational or corrective response. Informative responsive packaging is aimed at continuously monitoring the changes in food or environmental conditions and conveys this information to the users in real time. Meanwhile, packaging systems with the capacity to control contamination or deterioration are also of great interest. Encouragingly, corrective responsive packaging attempting to mitigate the adverse effects of condition fluctuations on food has been investigated. This packaging exerts its effects through the triggered release of active agents by environmental stimuli. In this review, informative and corrective responsive packaging is conceptualized clearly and concisely. The mechanism and characteristics of each type of packaging are discussed in depth. This review also summarized the latest research progress of responsive packaging and objectively appraised their advantages. Evidently, the mechanism through which packaging systems respond to microbial contamination and associated environmental factors was also highlighted. Moreover, risk concerns, related legislation, and consumer perspective in the application of responsive packaging are discussed as well. Broadly, this comprehensive review covering the latest information on responsive packaging aims to provide a timely reference for scientific research and offer guidance for presenting their applications in food industry., (© 2021 Institute of Food Technologists®.)