An NIR-responsive hydrogel loaded with polydeoxyribonucleotide nano-vectors for enhanced chronic wound healing.

Chronic diabetic wounds are difficult to treat due to imbalanced inflammatory responses, high blood glucose levels, and bacterial infections. Novel therapeutic approaches based on nucleic acid analogues have been proposed, with unique advantages in improving angiogenesis, increasing collagen synthesis, and exerting anti-inflammatory effects. However, the inherent electronegativity of nucleic acids makes them less susceptible to cellular uptake. In this paper, a kind of near infrared (NIR)-responsive nanocomposite hydrogel loaded with nucleic acid vectors was proposed for promoting wound healing. The redox system composed of molybdenum disulphide nanosheets (MoS2 NSs) initiated the copolymerization of quaternized chitosan containing double bonds and N-isopropylacrylamide (NIPAAm) to form the matrix. In addition, MoS2 NSs with photothermal conversion performance endow the nanocomposite hydrogel to have NIR-response property and act as physical crosslinking points in the matrix. Polydeoxyribonucleotides (PDRN), which have the effect of promoting wound healing, were made into nucleic acid vectors, and loaded into the NIR-responsive hydrogel. MoS2 NSs can convert NIR irradiation into heat, causing phase transitions of temperature-sensitive segments that trigger volume contraction of the hydrogel to extrude the nucleic acid vector. Promoting angiogenesis, slowing inflammation, and guiding tissue regeneration were demonstrated in the diabetic wound model treated with the NIR-responsive nanocomposite hydrogel.

Triboelectric Nanogenerator Made with Stretchable, Antibacterial Hydrogel Electrodes for Biomechanical Sensing.

Triboelectric nanogenerators (TENGs) have attracted widespread attention as a promising candidate for energy harvesting due to their flexibility and high power density. To meet diverse application scenarios, a highly stretchable (349%), conductive (1.87 S m-1), and antibacterial electrode composed of carbon quantum dots/LiCl/agar-polyacrylamide (CQDs/LiCl/agar-PAAm) dual-network (DN) hydrogel is developed for wearable TENGs. Notably, the concentration of agar alters the pore spacing and pore size of the DN hydrogel, thereby impacting the network cross-linking density and the migration of conductive ions (Li+ and Cl-). This variation further affects the mechanical strength and conductivity of the hydrogel electrode, thus modulating the mechanical stability and electrical output performance of the TENGs. With the optimal agar content, the tensile strength and conductivity of the hydrogel electrode increase by 211 and 719%, respectively. This enhancement ensures the stable output of TENGs during continuous operation (6000 cycles), with open-circuit voltage, short-circuit current, and transferred charge increasing by 200, 530, and 155%, respectively. Additionally, doping with CQDs enables the hydrogel electrode to effectively inhibit the Gram-negative bacterium Escherichia coli. Finally, the TENGs are utilized as a self-power smart ring for efficient and concise information transmission via Morse code. Consequently, this study introduces a creative approach for designing and implementing multifunctional, flexible wearable devices.

NIR-II-Responsive Hybrid System Achieves Cascade-Augmented Antitumor Immunity via Genetic Engineering of Both Bacteria and Tumor Cells.

The combination of nanoparticles and tumor-targeting bacteria for cancer immunotherapy can overcome the shortcomings of poor nanoparticle accumulation, limited penetration, and restricted distribution. However, it remains a great challenge for the hybrid system to improve therapeutic efficacy through the simultaneous and controllable regulation of immune cells and tumor cells. Herein, a hybrid therapeutic platform is rationally designed to achieve immune cascade-augmented cancer immunotherapy. To construct the hybrids, photothermal nanoparticles responsive to light in the second near-infrared (NIR-II) region are conjugated onto the surface of engineered bacteria through pH-responsive Schiff base bonds. Taking advantage of the hypoxia targeting and deep penetration characteristics of the bacteria, the hybrids can accumulate at tumor sites. Then nanoparticles detach from the bacteria to realize genetic engineering of tumor cells, which induces tumor cell apoptosis and down-regulate the expression of programmed cell death ligand 1 to alleviate immunosuppressive tumor microenvironment. The mild photothermal heating can not only induce tumor-associated antigen release, but also trigger sustainable expression of cytokine interleukin-2. Notably, a synergistic antitumor effect is achieved between the process of p53 transfection and NIR-II light-activated genetic engineering of bacteria. This work proposes a facile strategy for the construction of hybrid system to achieve cascade-augmented cancer immunotherapy.

Improved Cell Adhesion on Self-Assembled Chiral Nematic Cellulose Nanocrystal Films.

Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.

Prussian Blue-Assisted NIR Triggered In-Situ Polymerized Nanocomposite Hydrogel for Wound Repair.

Hydrogels are commonly used as wound dressings to help maintain a moist environment around the wound and isolate contaminants, thus promoting healing. For irregular wounds, the slow healing process and even infection may occur due to the inability of dressings to adhere well to the wound. Prussian blue (PB) is a metal-organic framework (MOF) material with excellent photothermal conversion and superior stability. In this paper, a kind of near-infrared (NIR) light triggered in-situ polymerized antimicrobial hydrogel was prepared. The free radical initiator was encapsulated in the hollow PB by a phase change material (PCM) to maintain stability. The raised temperature triggered by NIR induced the release and decomposition of the initiator. The matrix was formed by the cross-linking of double bonds on modified chitosan. The quaternary amine groups of modified chitosan and the photothermal properties of PB enhanced the antimicrobial properties of the hydrogel. High-quality wound healing was demonstrated in the whole skin defect model. This study provides a new reference for the preparation of in-situ polymerized hydrogel dressings for irregular wounds.

High-Performance W-Doped Bi0.5Sb1.5Te3 Flexible Thermoelectric Films and Generators.

Bi-Sb-Te-based thermoelectric materials have the best room-temperature thermoelectric properties, but their inherent brittleness and rigidity limit their application in the wearable field. In this study, W-doped p-type Bi0.5Sb1.5Te3 (W-BST) thin films were prepared using magnetron sputtering on polyimide substrates to create thermoelectric generators (TEGs). Bending tests showed that the thin film has excellent flexibility and mechanical durability, meeting the flexible requirements of wearable devices. W doping can significantly increase the carrier concentration, Seebeck coefficient, and electrical conductivity of BST thin films. At 300 K, the power factor of the W-BST film is 2.25 times higher than that of the undoped film, reaching 13.75 µW cm-1 K-2. First-principles calculations showed that W doping introduces significant impurity peaks in the bandgap, in which W d electrons remarkably hybridize with the Sb and Te p electrons, leading to an improved electrical conductivity of BST films. Furthermore, W doping significantly reduces the work function of BST films, thereby improving the carrier mobility. A TEG module fabricated from four layers of W-BST thin films achieved a maximum output power density of 6.91 mW cm-2 at a temperature difference of 60 K. Application tests showed that the flexible TEG module could power a portable clock using the temperature difference between body temperature and room temperature. At a medium temperature of 439 K, the assembled TEG module can provide a stable output voltage of 1.51 V to power a LED. This study demonstrates the feasibility of combining inorganic thermoelectric materials with flexible substrates to create high-performance flexible TEGs.

Thermoresponsive Gels with Embedded Starch Microspheres for Optimized Antibacterial and Hemostatic Properties.

Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents. In vitro and in vivo results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced in vitro hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.

One Endothelium-Targeted Combined Nucleic Acid Delivery System for Myocardial Infarction Therapy.

Acute myocardial infarction (MI) and ischemic heart disease are the leading causes of heart failure and mortality. Currently, research on MI treatment is focused on angiogenic and anti-inflammatory therapies. Although endothelial cells (ECs) are critical for triggering inflammation and angiogenesis, no approach has targeted them for the treatment of MI. In this study, we proposed a nonviral combined nucleic acid delivery system consisting of an EC-specific polycation (CRPPR-grafted ethanolamine-modified poly(glycidyl methacrylate), CPC) that can efficiently codeliver siR-ICAM1 and pCXCL12 for the treatment of MI. Animals treated with the combination therapy exhibited better cardiac function than those treated with each nucleic acid alone. In particular, the combination therapy of CPC/siR-ICAM1 and CPC/pCXCL12 significantly improved cardiac systolic function, anti-inflammatory responses, and angiogenesis compared to the control group. In conclusion, CPC-based combined gene delivery systems show impressive performance in the treatment of MI and provide a programmed strategy for the development of codelivery systems for various EC-related diseases.

Enhancing Tranexamic Acid Penetration through AQP-3 Protein Triggering via ZIF-8 Encapsulation for Melasma and Rosacea Therapy.

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches ≈25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration.

The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair.

Pelvic organ prolapse (POP) has a high incidence rate among Chinese women. Repeated mechanical stimulation is an important factor causing POP, but the injury mechanism has not yet been elucidated. The purpose of this study is to explore the related mechanisms of pelvic floor supporting tissue damage caused by mechanical force and the application of stem cell therapy. First, we obtained vaginal wall and sacral ligament tissue samples from clinical patients for examination. Pelvic floor support tissues of POP patients displayed high expression of inflammation and immune disorders. Then, we constructed a rat model of childbirth injury. In vivo and in vitro experiments investigated the key mechanism of pelvic floor support tissue injury caused by mechanical force. We discovered that after mechanical force, a large number of reactive oxygen species (ROS) and macrophages rapidly accumulated in pelvic floor tissues. ROS stimulated macrophages to produce NLRP3 inflammatory complex, induced the release of interleukin (IL-1ß) and pyroptosis and exacerbated the inflammatory state of damaged tissues, persisting chronic inflammation of fibroblasts in supporting tissues, thus causing the pelvic floor's extracellular matrix (ECM) collagen metabolic disorder. Resultingly impeding the repair process, thereby causing the onset and progression of the disease. Through their paracrine ability, we discovered that adipose mesenchymal stem cells (ADSCs) could inhibit this series of pathological processes and promote tissue repair, asserting a good therapeutic effect. Simultaneously, to overcome the low cell survival rate and poor therapeutic effect of directly injecting cells, we developed a ROS-responsive PVA@COLI hydrogel with ADSCs. The ROS-scavenging properties of the gel could reshape the site of inflammation injury, enhance cell survival, and play a role in subsequent treatment. The findings of this study could serve as a basis for early, targeted intervention therapy for POP and representing a promising approach.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.

Hydroxyl-rich branched polycations for nucleic acid delivery.

Recently, nucleic acid delivery has become an amazing route for the treatment of various malignant diseases, and polycationic vectors are attracting more and more attention among gene vectors. However, conventional polycationic vectors still face many obstacles in nucleic acid delivery, such as significant cytotoxicity, high protein absorption behavior, and unsatisfactory blood compatibility caused by a high positive charge density. To solve these problems, the fabrication of hydroxyl-rich branched polycationic vectors has been proposed. For the synthesis of hydroxyl-rich branched polycations, a one-pot method is considered as the preferred method due to its simple preparation process. In this review, typical one-pot methods for fabricating hydroxyl-rich polycations are presented. In particular, amine-epoxide ring-opening polymerization as a novel approach is mainly introduced. In addition, various therapeutic scenarios of hydroxyl-rich branched polycations via one-pot fabrication are also generalized. We believe that this review will motivate the optimized design of hydroxyl-rich branched polycations for potential nucleic acid delivery and their bio-applications.

A Janus Gelatin Sponge with a Procoagulant Nanoparticle-Embedded Surface for Coagulopathic Hemostasis.

Apart from the wide and safe application of natural polymer-based hemostatic materials/devices, it is still desirable to develop new types of hemostatic materials that can achieve both potent coagulopathic hemostasis and a facile preparation process. In this work, one Janus gelatin sponge (J-ZGS) is readily constructed for both coagulation-dependent and coagulopathic hemostasis by embedding zein nanoparticles on the surface of a self-prepared gelatin sponge (S-GS): zein nanoparticles were facilely prepared by an antisolvent method to achieve procoagulant blood-material interactions, while S-GS was prepared by freeze-drying a foaming gelatin solution. Due to the distinct secondary structure, the optimal zein nanoparticles possessed a higher in vitro hemostatic property than the pristine zein powder and other nanoparticles, the underlying mechanism of which was revealed as the superior RBC/platelet adhesion property in the presence/absence of plasma proteins. Compared with S-GS and a commercial gelatin sponge, J-ZGS achieved a significantly higher in vitro hemostatic property and similarly good blood compatibility/cytocompatibility. Moreover, in vivo artery-injury models confirmed the outstanding hemostatic performance of J-ZGS under both coagulation-dependent and coagulopathic conditions. Our work offers an appealing approach for developing potent hemostatic sponges from natural polymer-based nanoparticles that could be further extended to versatile hemostatic materials for coagulopathic hemostasis.

Genetically light-enhanced immunotherapy mediated by a fluorinated reduction-sensitive delivery system.

The lack of safe and efficient therapeutic agent delivery platforms restricts combined therapy's effect, and combined cancer therapy's multi-component delivery effect needs improvement. The novel gene delivery system SS-HPT-F/pMIP-3ß-KR was proposed to construct fluorine-containing degradable cationic polymers SS-HPT-F by a mild and simple amino-epoxy ring-opening reaction. By modifying the fluorinated alkyl chain, the delivery efficiency of the plasmid was greatly improved, and the cytoplasmic transport of biomolecules was completed. At the same time, a combination plasmid (MIP-3ß-KillerRed) was innovatively designed for the independent expression of immune and photodynamic proteins. Which was efficiently transported to the tumor site by SS-HPT-F. The MIP-3ß is expressed as an immune chemokine realize the immune mobilization behavior. The photosensitive protein KillerRed expressed in the tumor killed cancer cells under irradiation and released the exocrine immune factor MIP-3ß. The immunogenic cell death (ICD) produced by photodynamic therapy (PDT) also induced the immune response of the organism. The synergistic effect of PDT and MIP-3ß mobilized the immune properties of the organism, providing light-enhanced immune combination therapy against malignant tumors. Therefore, in subcutaneous tumor-bearing and metastatic animal models, the carrier tumor growth and mobilize organism produce an immune response without systemic toxicity. This work reports the first efficient gene delivery system that achieves light-enhanced immunotherapy.

Selenium in Photochemical Vapor Generation: Mechanism Study and Potential Nonchromatographic Speciation Analysis.

The mechanism of selenium in the UV photochemical vapor generation (PVG) process was investigated by the use of multiple analytical methods. It was found that the UV-induced photooxidation trapping of the generated volatile SeH2 should be responsible for the previous opinion of relative inertness of Se(VI) in PVG with formic acid. Furthermore, the formation of Se(IV) was found during the PVG process, and the comproportionation of Se(IV) with SeH2 and the photooxidation of Se(IV) into Se(VI) were investigated. Then, a preliminary model was proposed for the PVG process of Se(VI) and Se(IV) with low-molecular-weight organic acids. Then, a novel, simple, and green photocontrolled method without any photocatalyst was thus proposed for the nonchromatographic speciation analysis of Se(IV) and Se(VI), with a limit of detection of 0.2 and 5 ng/mL, respectively.

Biguanide chitosan microneedles with cell-free DNA scavenging ability for psoriasis therapy.

High levels of cell-free DNA (cfDNA) induce psoriasis. Currently, the treatment of psoriasis has the disadvantages of penetration difficulty, suppression of normal immunity, and skin irritation. In this study, biguanide chitosan microneedles (BGC-MNs) were prepared to treat psoriasis by removing cfDNA from the dermis through the skin barrier. The effects of chitosan with different bisguanidine contents on DNA-binding capacity, biocompatibility, and inflammation inhibition were compared, revealing that chitosan containing 20% bisguanidine (BGC2) was found to have the best overall performance. In vitro, BGC2 effectively cleared cfDNA and inhibited the production of inflammatory factors. BGC-MN made from BGC2 had good mechanical and solubility properties. In vivo, BGC-MNs cleared cfDNA, reduced the level of inflammatory factors in the dermis, and exerted a good therapeutic effect on mice with psoriasis. These results suggested that BGC-MNs provided a new approach to treating psoriasis in terms of scavenging cfDNA and exerting anti-inflammatory effects.

Rapid Regulation of Cardiomyocytes Adhesion on Substrates with Varied Modulus via Mechanical Cues.

In-depth understanding of the mechanisms underlying the adhesion of myocardial cells holds significant importance for the development of effective therapeutic biomaterials aimed at repairing damaged or pathological myocardial tissues. Herein, we present evidence that myocardial cells (H9C2) exhibit integrin-based mechanosensing during the initial stage of adhesion (within the first 2 h), enabling them to recognize and respond to variations in substrate stiffnesses. Moreover, the bioinformatics analysis of RNA transcriptome sequencing (RNA-seq) reveals that the gene expressions associated with initial stage focal adhesion (Ctgf, Cyr61, Amotl2, Prickle1, Serpine1, Akap12, Hbegf, and Nedd9) are up-regulated on substrates with elevated Young's modulus. The fluorescent immunostaining results also suggest that increased substrate stiffness enhances the expression of Y397-phosphorylated focal adhesion kinase (FAK Y397), talin, and vinculin and the assembly of F-actin in H9C2 cells, thereby facilitating the adhesion of myocardial cells on the substrate. Next, we utilize fluidic force microscopy (FluidFM)-based single-cell force spectroscopy (SCFS) to quantitatively evaluate the impact of substrate stiffness on the cell adhesion force and adhesion work, thus providing novel insights into the biomechanical regulation of initial cell adhesion. Our findings demonstrate that the maximum adhesion forces of myocardial cells exhibit a rise from 23.6 to 248.0 nN when exposed to substrates with different moduli. It is worth noting that once the αvß3 integrins are blocked, the disparities in the adhesion forces of myocardial cells on these substrates become negligible. These results exhibit remarkable sensitivity of myocardial cells to mechanical cues of the substrate, highlighting the role of αvß3 integrin as a biomechanical sensor for the regulation of cell adhesion. Overall, this work offers a prospective approach for the regulation of cell adhesion via integrin mechanosensing with potential practical applications in the areas of tissue engineering and regenerative medicine.

Controllable Star Cationic Poly(Disulfide)s Achieve Genetically Cascade Catalytic Therapy by Delivering Bifunctional Fusion Plasmids.

The absence of effective delivery vectors and suitable multifunctional plasmids limits cancer gene therapy development. The star cationic poly(disulfide)s with ß-cyclodextrin cores (termed ß-CD-g-PSSn ) for caveolae-mediated endocytosis are designed and prepared via mild and controllable disulfide exchange polymerization for high-efficacy cancer therapy. Then, ß-CD-g-PSSn /pDNA complexes are transported to the Golgi apparatus and endoplasmic reticulum. Disulfides in ß-CD-g-PSSn vectors are degraded by glutathione in tumor cells, which not only promotes intracellular pDNA release but also reduces in vitro and in vivo toxicity. One bifunctional fusion plasmid pCATKR, which expresses catalase (CAT) fused to KillerRed (KR) (CATKR) in the same target cell, is also proposed for genetically cascade catalytic therapy. When compared with pCAT-KR (plasmid expressing CAT and KR separately in the same cell), delivered pCATKR decomposes hydrogen peroxide, alleviates tumor hypoxia more effectively, generates stronger reactive oxygen species (ROS) capabilities under moderate irradiation, and leads to robust antitumor cascade photodynamic effects. These impressive results are attributed to fusion protein design, which shortens the distance between CAT and KR catalytic centers and leads to improved ROS production efficiency. This work provides a promising strategy by delivering a catalytic cascade functional plasmid via a high-performance vector with biodegradable and caveolae-mediated endocytosis characteristics.

Polysaccharide-based tumor microenvironment-responsive drug delivery systems for cancer therapy.

The biochemical indicators of tumor microenvironment (TME) that are different from normal tissues provide the possibility for constructing intelligent drug delivery systems (DDSs). Polysaccharides with good biocompatibility, biodegradability, and unique biological properties are ideal materials for constructing DDSs. Nanogels, micelles, organic-inorganic nanocomposites, hydrogels, and microneedles (MNs) are common polysaccharide-based DDSs. Polysaccharide-based DDSs enable precise control of drug delivery and release processes by incorporating TME-specific biochemical indicators. The classification and design strategies of polysaccharide-based TME-responsive DDSs are comprehensively reviewed. The advantages and challenges of current polysaccharide-based DDSs are summarized and the future directions of development are foreseen. The polysaccharide-based TME-responsive DDSs are expected to provide new strategies and solutions for cancer therapy and make important contributions to the realization of precision medicine.

Janus nanoparticles targeting extracellular polymeric substance achieve flexible elimination of drug-resistant biofilms.

Safe and efficient antibacterial materials are urgently needed to combat drug-resistant bacteria and biofilm-associated infections. The rational design of nanoparticles for flexible elimination of biofilms remains challenging. Herein, we propose the fabrication of Janus-structured nanoparticles targeting extracellular polymeric substance to achieve dispersion or near-infrared (NIR) light-activated photothermal elimination of drug-resistant biofilms, respectively. Asymmetrical Janus-structured dextran-bismuth selenide (Dex-BSe) nanoparticles are fabricated to exploit synergistic effects of both components. Interestingly, Janus Dex-BSe nanoparticles realize enhanced dispersal of biofilms over time. Alternatively, taking advantage of the preferential accumulation of nanoparticles at infection sites, the self-propelled active motion induced by the unique Janus structure enhances photothermal killing effect. The flexible application of Janus Dex-BSe nanoparticles for biofilm removal or NIR-triggered eradication in vivo is demonstrated by Staphylococcus aureus-infected mouse excisional wound model and abscess model, respectively. The developed Janus nanoplatform holds great promise for the efficient elimination of drug-resistant biofilms in diverse antibacterial scenarios.