Excessive reactive oxygen species (ROS) accumulation and an imbalance in M1/M2 macrophage polarization are major contributors to impaired diabetic wound healing. Based on these findings, we developed an injectable hydrogel dressing capable of modulating the wound microenvironment. 1,4-Butanediol diglycidyl ether (BDDE) was linked to Dendrobium officinale polysaccharide (DOP) and sodium polyacrylate (PAAS) via ether bonds to form the DOP-BDDE-PAAS (DBP). 3-Aminophenylboronic acid (PBA) was linked to hyaluronic acid (HA) via amide bonds and to resveratrol (Res) via boronate bonds, yielding the HA-PBA-Res (HPR). The DBP and HPR components were then combined to form the DBPHPR hydrogel network. The hydrogel exhibited suitable injectability and self-healing properties. In vitro experiments demonstrated that the hydrogel released Res in response to high ROS or glucose concentrations. Through the synergistic effects of DOP and Res, the hydrogel promoted fibroblast proliferation and migration, effectively scavenged excessive ROS, and regulated macrophage polarization toward the M2 phenotype. In a full-thickness skin defect model in mice, the DBPHPR hydrogel reduced inflammation, promoted wound epithelialization, accelerated collagen deposition, and enhanced overall wound healing. In summary, the plant polysaccharide-bioactive small-molecule hydrogel developed via dynamic covalent bonding offers a strategy for diabetic wound dressings and has promising potential for clinical application.

Impaired M2 macrophage polarization, excessive reactive oxygen species (ROS) production, and impaired angiogenesis are major barriers to effective wound healing in diabetes. Although nanoparticle-loaded hydrogels show great therapeutic potential, many existing nanoparticles have drawbacks such as low drug-loading capacity, cytotoxicity, poor stability, slow degradation. Herein, we used cystine dihydrochloride as a linker to conjugate oxidized Ganoderma lucidum polysaccharide (OGLP) with Ferulic Acid (FA) to successfully synthesize carrier-free Ganoderma lucidum polysaccharide-Ferulic acid nanoparticles (GFNPs) via precipitation. The GFNPs were subsequently co-loaded with recombinant human epidermal growth factor (rhEGF) into a hydrogel (CPP) matrix composed of chitosan and poloxamer (P407 and P188), a thermosensitive hydrogel composed of CPP@GFNPs and rhEGF has been obtained. GFNPs exhibit excellent in vitro and in vivo ROS-scavenging performance, promote M2 macrophage polarization, and exhibit strong antibacterial effects even at low doses. Furthermore, GFNPs can synergistically interact with rhEGF to promote the proliferation, migration, and angiogenesis of fibroblasts and human umbilical vein endothelial cells. In a murine model simulating diabetic wounds, the CPP@GFNPs & rhEGF hydrogel demonstrated substantial capacities for reducing inflammation, stimulating angiogenesis, and supporting tissue repair. In summary, this thermosensitive hydrogel wound dressing, which incorporates carrier-free traditional Chinese medicine polysaccharide-polyphenol nanoparticles and growth factors, represents a promising strategy for diabetic wound repair.

Elevated oxidative stress, tissue hypoxia, imbalanced macrophage polarization, and impaired angiogenesis are major factors that contribute to the poor healing of diabetic wounds. Traditional wound dressings often lack specific functions and are insufficient for addressing the pathological complexity of diabetic wounds. Here, we developed a hydrogel dressing based on multiple synergistic effects. This dressing comprises manganese dioxide nanosheets (MnO2 NSs) and recombinant human epidermal growth factor (rhEGF) loaded into a semi-interpenetrating hydrogel network with oxidized ginseng polysaccharide (OGPS), carboxymethyl chitosan (CMC), and sodium polyacrylate (PAAS) as the backbone materials, resulting in a CMC-OGPS/PAAS@MnO2 NSs/rhEGF hydrogel. In vitro experiments revealed that OGPS and MnO2 NSs synergistically scavenge intracellular reactive oxygen species (ROS) and that OGPS and rhEGF synergistically promote the proliferation and migration of L929 cells and tube formation by human umbilical vein endothelial cells (HUVECs). OGPS and MnO2 NSs also exhibited synergistic bactericidal activity. In vivo experiments in mice revealed that this hydrogel can reduce inflammation in wound tissue; increase oxygenation levels; promote angiogenesis, epidermal growth and collagen deposition; and accelerate wound repair in diabetic patients. This study provides a promising solution for the application of ginseng polysaccharides.

Remodeling the immune microenvironment and scavenging excess reactive oxygen species (ROS) are considered effective strategies for treating rheumatoid arthritis (RA). Methotrexate (MTX), a first-line drug, can correct the imbalance between helper T-cell type 17 and regulatory T cells (Th17/Treg) and inhibit the proliferation and migration of fibroblast-like synoviocytes (FLSs). However, it lacks antioxidant and macrophage regulatory functions, is prone to systemic toxicity, and has poor solubility. In this study, MTX and oxidized Bletilla striata polysaccharide (OBSP) were conjugated and self-assembled into MTX-ss-OBSP NPs via disulfide bonds to integrate macrophage-polarizing and antioxidant activities. These nanoparticles were loaded into a novel ROS-responsive oxidized hyaluronic acid-3-aminophenylboronic acid-hyaluronic acid (OHA-PBA-HA) hydrogel, yielding MTX-ss-OBSP NPs@OHA-PBA-HA. This injectable hydrogel exhibits ROS-triggered drug release, reduces ROS levels, promotes M2 macrophage polarization, and modulates cytokine secretion (decreasing IL-6/TNF-α; increasing IL-10). In vivo experiments demonstrated that the hydrogel blocks bone erosion, inhibits synovial inflammation, protects cartilage, and regulates M1/M2 and Th17/Treg balances while significantly reducing MTX-induced hepatotoxicity and nephrotoxicity. Compared with free MTX, this nanoparticle-loaded hydrogel accelerates the resolution of RA inflammation with superior safety. Therefore, this responsive hydrogel system represents a promising candidate for clinical RA treatment by integrating immune remodeling and antioxidant therapy.

Nanomaterials have demonstrated remarkable therapeutic potential in the realm of anti-tumor research, attributed to their unique physicochemical properties. These properties endow nanomaterials with significant efficacy in oncology applications. Nevertheless, as foreign entities, they are susceptible to immune system recognition and subsequent clearance, presenting a substantial obstacle to the efficient delivery of drugs to tumor sites via nanocarriers. Cholesterol (Chol), being an endogenous compound within the body, bypasses this immune surveillance, ensuring biocompatibility and evading carrier drug elimination by the immune system. In our experimental setup, we devised the Dox/MWCNTs-Chol delivery platform, comprising multi-walled carbon nanotubes (MWCNTs) encapsulating Doxorubicin (Dox), with its surface further functionalized with Chol. Remarkably, this system enables synergistic therapy through the integration of photothermal therapy (PTT) and chemotherapy, exhibiting robust cellular uptake in vitro and exceptional tumor homing capabilities. Chol, acknowledged explicitly by the low-density lipoprotein receptor (LDLR), facilitates cellular entry via endocytosis, subsequently shedding its load within lysosomes where free Chol is liberated. This design capitalizes on Chol's ability to trigger the specific release of Dox in the acidic tumor microenvironment. At the same time, the thermal damage inflicted by MWCNTs under laser activation enhances drug internalization and bolsters accumulation at the tumor site. Consequently, Dox/MWCNTs-Chol orchestrates a cascading anti-tumor effect, leveraging a bionic approach that combines targeted chemotherapy with phototherapy. This study thus contributes a novel blueprint for augmenting tumor-specific delivery efficiency and mitigating the adverse side effects associated with targeted therapies.

The Stimulator of Interferon Genes (STING) pathway crucially modulates antitumor immunity and has therapeutic potential in aggressive triple-negative breast cancer (TNBC). Agonist-mediated STING activation triggers interferon-signaling cascades, which amplifies immune responses and enhances antitumor capabilities. Adjunctively, photothermal therapy (PTT) utilizes localized hyperthermia for tumor ablation and concurrently elicits immunogenic cell death (ICD), releases tumor-associated antigens, and activates acquired immune responses. We used an amphiphilic carrier material (PEI-GCP(Z)/mPEG) to coload cyanine dye (IR783) and the STING agonist (MSA-2), which self-assembled into the nanoparticle (PMI) and conferred three therapeutic advantages: (1) PTT-induced tumor-cell death and release of tumor-associated antigens; (2) STING agonist-based activation of innate immunity and enhanced dendritic cell maturation and antigen presentation; and (3) significantly improved cytotoxic T-lymphocyte responses with immune checkpoint blockade and nanoparticle-aided photothermal-immunotherapy. We evaluated the cellular synergistic antitumor effects in vitro. In a bilateral breast tumor model, after intravenous injection, PMI accumulated in tumors and induced significant ICD after laser irradiation, promoted antigen-presenting cell maturation, and activated cytotoxic T-cell antitumor-killing effects. PMI-anti-PD-L1 antibody blockade inhibited distant tumor growth through an excellent antitumor immune response. Combining STING pathway activation with PTT to achieve robust antitumor immunity offers an effective approach to TNBC therapy.

Nanoparticle-targeted formulations are crucial for mitigating the cardiotoxicity, hepatotoxicity, and nephrotoxicity associated with Doxorubicin (Dox) in triple-negative breast cancer (TNBC) treatment. However, nanoparticles are readily recognized and cleared by the immune system, limiting their targeting efficiency. To overcome this limitation, we developed a biomimetic nanodrug delivery system that exploits the elevated cholesterol demand of tumor cells and the immune-evasive properties of endogenous cholesterol. The system employs cholesterol-modified core-shell mesoporous silica (CSMSN) nanoparticles (Chol/Dox-CSMSN), in which Dox is encapsulated within the core and cholesterol coats the exterior. This design enables active targeting through the low-density lipoprotein receptor (LDLR)-mediated cholesterol metabolism pathway, markedly enhancing tumor-specific drug accumulation. Experimental results demonstrated that cellular uptake of Chol/Dox-CSMSN was approximately twofold higher than that of Dox-CSMSN. Following lysosomal uptake, Dox was released in response to glucosylceramidase activity, achieving a cumulative release of 70 % within 48 h. Consequently, the IC50 value for 4T1 cells decreased by 6.07-fold, and cell migration was significantly suppressed, with a scratch migration rate of 15.7 %. Biosafety assessments revealed a hemolysis rate below 5 %, no histopathological abnormalities in major organs, and while blood biomarkers remained comparable to control levels (p > 0.05). This biomimetic nanodelivery platform, leveraging endogenous metabolic pathways for targeted drug transport, provides a promising strategy for safe, efficient and low-toxicity chemotherapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and in China, Most patients are already in an advanced stage at the time of diagnosis, and the chance of complete surgical resection is lost, therefore, drug treatment is particularly important. Angelica sinensis polysaccharide (ASP) has natural liver-targeting properties, berberine (BBR) is a lipophilic cation with anticancer activities and mitochondrial-targeting properties, and honokiol (HNK) has mitochondria-dependent anticancer effects against cancer. Therefore, the aim of the present work was to synthesize Angelica sinensis polysaccharide-berberineamphiphilic polymer (ASP-SS-BBR) loaded with HNK to prepare the micelles ASP-BBR-PM@HNK to improve the hepatic targeting ability of the nanoparticles and the mitochondrial targeting ability in HCC cells and to enhance the anti-HCC effect of HNK. The findings of this study demonstrate the successful synthesis of ASP-BBR-PM@HNK, characterized by a particle size of 48.6 ± 1.13 nm. The formulation exhibits commendable stability, a sustained-release profile, and the capability for glutathione (GSH)-responsive release. ASP-BBR-PM@HNK is efficiently internalized by HepG2 cells, exhibiting the highest rate of cell inhibition. Additionally, the use of Gal and Man as receptor blockers confirmed the formulation’s superior targeting capabilities, including exceptional mitochondrial targeting. Subsequent in vivo experiments employing BALB/c nude mice as a model further corroborated these experimental outcomes. This research has successfully developed an effective natural dual-targeting system, offering a novel approach for the precise treatment of liver cancer.

The mechanism of the difficulty in healing of diabetic foot ulcers (DFUs) involves imbalanced macrophage polarization, excessive accumulation of reactive oxygen species (ROS), and local hypoxic microenvironment in the wound. Therefore, regulating macrophage polarization to M2, removing excessive reactive oxygen species, and improving tissue oxygen supply have become key therapeutic strategies to promote the healing of DFUs. In this study, a Janus nanofibrous membrane (Janus NFM) wound dressing composed of a hydrophilic layer (poly(vinyl alcohol)-chitosan-Dendrobium officinale polysaccharide) and a hydrophobic layer (polycaprolactone-calcium peroxide) was designed. DOP was esterified with adipic acid (AA) to form the backbone material while functioning therapeutically. Janus NFM has a porous microstructure and excellent physical and chemical properties. The optimized electrospinning process improves the stability of the interface between the hydrophilic and hydrophobic layers and the controllability of oxygen release. D. officinale polysaccharide has significant ROS scavenging ability and can induce macrophage polarization to the anti-inflammatory and pro-repair M2 phenotype; through a hydrolysis reaction, calcium peroxide constantly releases oxygen, significantly reducing the wound's hypoxic condition, and demonstrating broad-spectrum antibacterial activity. Janus NFM exhibits good biocompatibility both in vitro and in vivo. Animal experiments showed that the Janus NFM treatment group significantly promoted wound angiogenesis and collagen deposition compared with the control group, ultimately accelerating the wound closure rate (achieved a healing rate of 99.1 +/- 0.5% (mean +/- SD) by day 14). In summary, Janus NFM exhibits synergistic therapeutic advantages by maintaining steady-state ROS, balancing macrophage polarization and continuous oxygen delivery, and has potential clinical translational value.

Local anesthetics have been widely used in clinical analgesia due to their ability to provide effective regional pain management. Accurate measurement of local anesthetics in body fluids is crucial for ensuring patient medication safety and optimizing therapeutic efficacy. Herein, we present a convenient, economical, sensitive, and efficient TLC-SERS method for multiplex determination of six kinds of anesthetics (pro) in human plasma, including procaine hydrochloride (Pro), tetracaine hydrochloride (Tet), dibucaine (Dib), mepivacaine hydrochloride (Mep), lidocaine hydrochloride (Lid), and ropivacaine hydrochloride (Rop). The TLC method was adopted to separate six local anesthetics effectively. In order to improve the sensitivity, TLC spots were concentrated into smaller ones using methanol through solvent-driven enrichment, then Ag NPs staining was applied to enriched spots for a strong and unique SERS response of each anesthetic. As a result, linear calibration curves of SERS intensity ratio versus negative logarithm of spotting amounts sampled on TLC plates were obtained, along with the lowest detectable amounts in this study were 1 ng (Pro), 10 pg (Tet), 10 ng (Dib), 50 ng (Mep), 50 ng (Lid), and 0.1 μg (Rop), which were up to 2 × 104 times more sensitive than our previous TLC-Raman method. Moreover, the method was successfully applied to human plasma samples, demonstrating the feasibility and potential for multiplex analysis of local anesthetics in clinical practice, criminal forensics, and aquaculture.

The chemotherapy effect is generally affected by the premature release of nanoplatform and multi-drug resistance. In light of the advantages of photothermal therapy (PTT) and cascade catalytic therapy, we developed a multi-sensitive drug delivery system (MHC-Au-P) by grafting the gold NPs onto the opening of mesoporous hollow carbon nanoparticles (MHC) using gold sulfur bonds. MHC had excellent photothermal conversion efficiency and GSH consumption function, serving as a carrier for highly loading doxorubicin (DOX). The gold NPs were used due to their diverse functions, including smart switches to block the release of harmful substances, PTT agents to enhance the thermogenic effect of MHC, and nanozymes with GOx-like activity. When physical conditions are normal, gold-sulfur bond, which serves as the link between MHC carrier and Au-NPs, was stable, but the stability will decrease when glutathione (GSH) concentration in tumor cytoplasm was high. The DOX loaded D@MHC-Au-P can be rapidly decomposed into DOX@MHC and gold NPs at high GSH concentration after reaching the tumor microenvironment. The separated Au-NPs was capable of catalyzing the oxidation of glucose to H2O2 and glucuronic acid, providing raw materials and optimizing conditions for the POD-like enzyme catalysis of MHC. Under near-infrared irradiation, the release rate of drugs was further accelerated, GSH con-sumption rate, the catalytic rate of Au-NPs and MHC were further improved. The synergistic effect of D@MHC-Au-P for PTT-enhanced cascade catalytic therapy and chemotherapy was realized in vivo and in vitro with a combination index of 0.62. Therefore, D@MHC-Au-P can be used as a smart nanocarrier for photothermal-enhanced synergistic cascade catalysis and chemotherapy.

Liposome has the ability to co-encapsulate hydrophobic and hydrophilic bioactive compounds due to its unique structure consisting of both aqueous core and lipid bilayer. The simultaneous delivery of bioactive compounds often brings synergistic effects and more health benefits. This article discusses the recent progress on the liposomal co-delivery systems for various combinations of bioactive compounds, including two hydrophobic bioactives, two hydrophilic bioactives, and hydrophobic/hydrophilic bioactives, as well as to combine biopolymer modification. The co-encapsulation mechanisms, influencing factors, and functional food applications are illustrated. The liposomal co-encapsulation has shown the synergistic effects on the stability, antioxidant activity, anti-inflammatory activity, and controlled release of bioactive compounds. The advantages and limitations associated with the co-delivery efficiency of liposomes are also highlighted.

Osteosarcoma (OS) is the predominant bone tumor affecting pediatric and adolescent populations. The standard treatment regimen involves preoperative chemotherapy, surgical intervention, and postoperative chemotherapy. Methotrexate (MTX) serves as the first-line pharmacological agent for OS treatment; however, the emergence of tumor resistance to chemotherapeutic agents poses a significant challenge. Cucurbitacin B (CuB) exhibits intrinsic anti-OS properties and can synergistically enhance OS suppression by reversing drug resistance and augmenting the therapeutic effects of MTX. Nevertheless, the clinical application of CuB and MTX is hindered by their low aqueous solubility, necessitating the development of an effective drug delivery system to precisely target tumor tissues and maximize therapeutic efficacy. Consequently, this study focuses on the development of a nanostructured lipid carrier (NLC) co-loaded with MTX and CuB (MTX-CuB-NLC) to address these limitations. MTX-CuB-NLC is characterized as a spherical nanoparticle with a mean particle size of 44.13 ± 1.40 nm, a polydispersity index (PDI) of 0.279 ± 0.120, and a zeta potential of -17.10 ± 4.98 mV. The encapsulation efficiency (EE%) and drug loading (DL%) were determined to be 61.03 ± 2.40 % and 0.25 ± 0.02 % for MTX, and 81.02 ± 1.61 % and 0.23 ± 0.02 % for CuB, respectively. The formulation demonstrated substantial storage stability over a 14-day period. In vitro release studies indicated that MTX-CuB-NLC possesses sustained release capabilities. Furthermore, the nanoparticle exhibited significantly enhanced uptake and cytotoxicity against U-2 OS cells compared to the free drug. Notably, MTX-CuB-NLC displayed pronounced cytotoxic effects on methotrexate-resistant U-2 OS cells (U-2 OS/MTX), underscoring its potential to induce apoptosis and circumvent multidrug resistance in these cells. In an OS nude mouse model exhibiting drug resistance, MTX-CuB-NLC demonstrated superior tumor targeting and suppression efficacy. This research has culminated in the development of an effective continuous drug delivery system for osteosarcoma, presenting a promising strategy to combat drug resistance in this malignancy.

To enhance the efficacy of hecogenin (HCG) against breast cancer cells, we designed and synthesized two series of new HCG‑nitrogen mustard hybrids (4a-4f and 5a-5f) by linking benzoic acid mustard or chlorambucil to HCG via amino acid residues. The derivatives were screened to assess their anti-proliferative activity against three human breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7), and one normal human breast MCF-10A cell line. Among the synthesized compounds, hybrid 5d exhibited the most potent anti-proliferative activity against the triple-negative breast cancer cell line MDA-MB-231, with an IC50 value of 2.2 μM. This represents a 27.2-fold increase in potency compared to the parent compound HCG (IC50 = 59.8 μM). Furthermore, hybrid 5d exhibited low toxicity toward MCF-10A cells (IC50 > 100 μM), indicating certain selectivity. Notably, the transwell migration assay revealed that hybrid 5d significantly inhibited the invasion of MDA-MB-231 cells. Preliminary mechanism studies indicated that hybrid 5d induced G2/M phase arrest and apoptosis via the mitochondria-related apoptotic pathway, as well as caused DNA damage. Collectively, these results suggest that hybrid 5d is a promising lead compound for anti-breast cancer research worthy of further investigation.

Hypochlorous acid (HClO) plays a crucial role in public and personal hygiene. However, the residual presence of HClO in water may pose potential risks to human health. Concurrently, HClO is indispensable in biological systems. Excessive accumulation of HClO can induce oxidative stress, mitochondrial dysfunction, and inflammatory responses, potentially leading to liver damage and even cancer. In this study, we integrated methylene blue (MB) with a benzothiazole derivative (BHP-OH) to synthesize a novel, highly selective dual-channel responsive fluorescent probe, MBT-PC. This probe is capable of rapidly detecting abnormal fluctuations in HClO concentrations in both environmental and biological settings. The uniqueness of the MBT-PC probe lies in its significant fluorescence enhancement in both the blue and red channels, with each channel providing an independent response to improve detection accuracy. Moreover, MBT-PC demonstrates exceptional selectivity, rapid response time (∼30 s), and an ultra-low detection limit in the blue fluorescence channel (18.7 nM), highlighting its superior sensing capabilities. Importantly, the MBT-PC probe not only enables rapid and safe monitoring of water quality safety through visible blue fluorescence changes on paper test strips and agarose sensing platforms, but also demonstrates excellent performance in HClO imaging in living cells, solid tumors, and liver injury models.

Acute lung injury (ALI) is a clinically prevalent inflammatory disorder that still needs to be developed with more accurate diagnostic biomarkers and more satisfactory therapies. This study intended to explore the therapeutic material basis and molecular mechanisms of a classical traditional Chinese medicinal prescription, Sang Ju Yin (SJY), against ALI, focusing on the chemical components of formula composition, the disturbance of host genes/metabolites and the dysbiosis of intestinal flora. First, based on liquid chromatography-mass spectrometry (LC-MS) component analysis, 212 in vitro and 44 in vivo compounds were identified respectively in SJY. Then, network pharmacology was adopted to calculate potential anti-ALI compounds in SJY and predict that CXCR2, PI3K-Akt signaling and arachidonic acid (AA) metabolism could be potential targets. Subsequently, integrative multi-omics techniques were employed to elaborate deeper systematic molecular mechanisms. Metabolomic data combining both 1H NMR and LC-MS techniques illustrated that 146 pulmonary and 75 fecal biomarkers, associated with AA and other metabolisms, were recuperated by SJY’s intervention. Transcriptomic analyses suggested that SJY could significantly regulate genes and signaling pathways involved with inflammation and apoptosis, such as PI3K-Akt. Further the obtained key targets (IL-10, LCAT, CXCR2 and C5) were verified by qRT-PCR and their relative compound-target interaction were validated by molecular docking. Notably, the disturbance of intestinal microbial community (such as the abundance of Lactobacillus, etc.) was detected through 16S rRNA gene sequencing, that could be effectively reshaped by SJY. Collectively, our integrated work showed SJY could regulate the crosstalk of metabolite-target-pathway-microflora along the gut-microbiota-lung axis on the whole. Noteworthy, our study provided fundamental and new insights into how molecular networks connected different types of components, genes, metabolites, microbes and potential pathways to map an endogenous functional landscape for clinical ALI diagnosis and SJY application.

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

Oxidative stress and excessive hypoxia are two key factors hindering diabetic wound healing. Prussian blue nanoparticles (PBNPs) and calcium peroxide (CPO) possess the characteristics of scavenging reactive oxygen species (ROS) and chemically generating oxygen respectively, and both can be used as biomedical materials. However, when the two substances coexist in the aqueous media, Prussian blue undergoes decomposition. In this study, gelatin/carboxymethyl chitosan @PBNP hydrogel and gelatin/carboxymethyl chitosan@CPO hydrogel were prepared separately and combined into concentric circular structures. The results showed that the combination of two hydrogels has good properties for swelling, adhesion, in vitro antioxidant, scavenging intracellular ROS, downregulating tumor necrosis factor-alpha (TNF-alpha), and enhancing the proliferation and migration of fibroblasts. In a diabetic mouse wound model, the combined application group shortened wound healing time, promoted growth of granulation tissues, and accelerated collagen formation compared with a single hydrogel treatment. The combined use of the two drug-loaded hydrogels has potential application in promoting diabetic wound repair.

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5–10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues.

Impaired macrophage polarization or the high levels of reactive oxygen species (ROS) produced by high glucose conditions and bacterial infection are the primary factors that make healing diabetic wounds difficult. Here, we prepared an OGLP-CMC/SA hydrogel with a double network structure that was synthesized with oxidized Ganoderma lucidum polysaccharide (OGLP), sodium alginate (SA) and carboxymethyl chitosan (CMC) as the matrix. The results showed that the OGLP-CMC/SA hydrogel had good mechanical properties, tissue adhesion, oxidation resistance and biocompatibility. Moreover, the hydrogel could effectively improve the proliferation and migration of fibroblasts, also can enhance antibacterial properties. We found that the OGLP-CMC/SA hydrogel can promote the polarization of M1 macrophages towards the M2 and decrease intracellular ROS levels, effectively reduce the inflammatory response, and promote epidermal growth, the development of skin appendages and collagen deposition in wounds, which hasten diabetic wound healing. Therefore, using this versatile biologically active new hydrogel network constructed with OGLP provides a promising therapeutic strategy for chronic diabetic wound repair.