Mesoporous Polydopamine Research Articles

Photothermal-Triggered Extracellular Matrix Clearance and Dendritic Cell Maturation for Enhanced Osteosarcoma Immunotherapy.

Osteosarcoma, a predominant malignant tumor among adolescents, exhibits high mortality and suboptimal immunotherapy efficacy due to a collagen-dense extracellular matrix (ECM) that hinders cytotoxic T lymphocyte (CTL) infiltration. Herein, we developed mesoporous polydopamine (MPDA) nanoparticles encapsulating bromelain and the immune adjuvant R848 (M@B/R), aimed at enhancing photothermal immunotherapy. These nanoparticles efficiently accumulate at the tumor site following injection. Upon near-infrared (NIR) light irradiation, photothermal therapy (PTT) induces immunogenic cell death in tumor cells and, with the aid of R848, efficiently promotes dendritic cell maturation, activating antitumor immunity and leading to CTL infiltration into the tumor. Concurrently, NIR-induced heating activates bromelain, resulting in ECM degradation and improved CTL penetration into the tumor. Our in vivo evaluations demonstrate potent antitumor effects in osteosarcoma-bearing mice. This integrated approach offers a promising strategy for overcoming physical barriers in ECM-rich tumors, marking a significant advancement in the treatment of osteosarcoma.

Mitochondrial-Targeting Mesoporous Polydopamine Nanoparticles for Reducing Kidney Injury Caused by Depleted Uranium.

Depleted uranium (DU), when accidentally released from the nuclear industry, can enter the human body and cause kidney damage, as DU induces oxidative damage and apoptosis through mitochondrial pathways and inflammatory reactions. The existing nanoparticles used to treat DU injury have low bioavailability and poor targeting. In this study, mesoporous polydopamine (MPDA), poly-(ethylene glycol) (PEG), and triphenylphosphonium (TPP) are combined to develop a novel mitochondrion-targeting bifunctional nanoparticle, MPDA-PEG-TPP, and confirm that it can protect the kidneys from DU. This study demonstrates the high selectivity of MPDA-PEG-TPP for uranyl in uranyl chelate assays and its promising efficiency in uranyl sequestration from the kidneys, lungs, and femurs, following immediate or delayed administration of MPDA-PEG-TPP nanoparticles. In vitro assays confirm its efficiency in removing reactive oxygen species and targeting the mitochondria. In addition, in vitro and in vivo assays confirm that MPDA-PEG-TPP can reduce mitochondrial dysfunction and ameliorate kidney injury. These results suggest that MPDA-PEG-TPP is a valuable agent for ameliorating the DU-induced kidney injury.

Coordination-Driven in Situ Grown Copper Peroxide in Mesoporous Dopamine with Self-Supplied H2O2 for Synergistic Enhanced PTT/CDT Antibacterial Treatment and Wound Healing.

As antibiotic resistance increases, alternative antimicrobial methods become essential. Chemical dynamics therapy (CDT) utilizing copper peroxide (CuO2) nanodots shows significant potential in antibacterial applications due to its ability to self-supply hydrogen peroxide (H2O2) on its own. This characteristic effectively addresses the challenges of low H2O2 levels and high glutathione (GSH) expression in the bacterial infection microenvironment. However, its tendency to aggregate and instability greatly affect its effectiveness. Therefore, this study developed a coordination-driven strategy to prepare copper peroxide-loaded mesoporous polydopamine nanomaterials (CuO2@MPDA) through in situ growth of CuO2 in mesoporous polydopamine utilizing the chelating interaction between amino and catechol structures of MPDA with copper ions. This strategy not only ensures that copper peroxide is evenly distributed within the pores of mesoporous polydopamine but also protects it through the shielding effect of pores, greatly enhancing its dispersibility and stability. More notably, the loading of CuO2 enhances the photothermal performance of MPDA by broadening its light absorption range, and MPDA-mediated photothermal therapy (PTT) can accelerate CuO2 to produce more hydroxyl radicals by speeding up chemical reactions, resulting in a combined boost in PTT and CDT. The developed CuO2@MPDA nanomaterials at very low concentrations exhibit improved antibacterial efficiency both in vitro and in vivo. Overall, this study provides an innovative strategy to construct an antibacterial nanoplatform for synergistically enhanced PTT/CDT dual-mode antibacterial treatment, exhibiting great potential for future biomedical applications.

Myocardial cell mitochondria-targeted mesoporous polydopamine nanoparticles eliminate inflammatory damage in cardiovascular disease

Excess reactive oxide species (ROS) is a direct factor in myocardial injury death, thus anti-oxidant therapy is a necessary measure to prevent rapid death of cardiomyocyte cell. Cysteine (Cys) is a potent antioxidant but easily become instability because of the hyperactivity. Therefore, in order to protect the the stability of Cys, we according to the mitochondria are the main sites of ROS production, utilized the loading and ROS scavenging capacity of mesoporous polydopamine (mPDA) constructed a nanosystem targeting mitochondria with effectively ROS elimination capability by loading cysteine (Cys-mPDA@TPP). The mesoporous structure of mPDA effectively inhibited the advance reaction and hyperactivity of Cys, thus effectively improving its stability that reached the double-collaborative treatment excess ROS. In particular, Cys-mPDA@TPP achieved directly reacting with ROS in mitochondria under the targeting of triphenylphosphine (TPP), not only enhancing the elimination efficiency of ROS, but also preventing mitochondrial dysfunction of monocyte-macrophage. Furthermore, with double-collaborative ROS elimination, Cys-mPDA@TPP effectively prevent the damage of cardiomyocyte cell through inhibiting macrophage inflammatory response. Therefore, this study provides a new therapeutic strategy for myocardial inflammatory injury.

Enhancing Water Lubrication in UHMWPE Using Mesoporous Polydopamine Nanoparticles: A Strategy to Mitigate Frictional Vibration.

Establishing a persistent lubrication mechanism and a durable tribo-film on contact surfaces is identified as crucial for improving the tribology and vibration characteristics of polymer materials under water-lubricated conditions. This study focuses on enhancing tribological performance and reducing frictional vibrations in ultrahigh molecular weight polyethylene (UHMWPE) through the incorporation of mesoporous polydopamine (MPDA) nanoparticles. In the experiments, MPDA nanoparticles were synthesized and blended with UHMWPE to create UHMWPE/MPDA composites. The interactions between these composites and zirconia (ZrO2) ceramic balls under water lubrication were examined. The results show that when the MPDA content of the composite is 1.5 wt %, the coefficient of friction and wear rate are reduced by 40% and 52% compared with those of pure UHMWPE, respectively. This notable enhancement helped to mitigate friction-induced vibrations, particularly those caused by intermittent sticking and slipping motions. MPDA nanoparticles were shown to act as reservoirs for water, releasing and replenishing water based on the loading conditions, which sustained continuous water-based lubrication at the composite surfaces. Additionally, the surface deformation behavior of the composite material is significantly weakened, which provides a more stable friction surface. This work introduces a novel approach to enhance the interface stability of polymers in water-lubricated environments, offering guidance for developing advanced materials and reducing friction and wear in engineering applications.

Toxicity and Oxidative Stress Biomarkers in the Organs of Mice Treated with Mesoporous Polydopamine Nanoparticles Modified with Iron and Coated with Cancer Cell Membrane.

Polydopamine nanoparticles (PDA NPs) have great potential in medicine. Their applications being widely investigated in cancer therapy, imaging, chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and tissue repair. The aim of our study was to assess the in vivo toxicity and changes in oxidative stress biomarkers in organs of animals treated with mesoporous PDA NPs modified with iron (MPDAFe NPs), coated with the cancer cell membrane and loaded with doxorubicin (DOX), and subsequently subjected to PTT. Liver and kidney homogenates were obtained from BALB/c nude mice with xenograft HepG2 human hepatoma cells, treated with iron modified mesoporous PDA nanoparticles, coated with the cancer cell membrane and loaded with doxorubicin (MPDAFe@DOX@Mem NPs), and subjected to PTT. These samples were used for histological evaluation and measurement of oxidative stress biomarkers, including total protein (TP), reduced glutathione (GSH), nitric oxide (NO), S-nitrosothiols (RSNO), thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD). In the kidney, MPDAFe@DOX@Mem NPs in combination with PTT increased GSH (43%), TBARS (32%), and CAT (27%), while SOD decreased by 20% compared to the control group. Additionally, CAT activity in the liver increased by 79%. Significant differences in oxidative stress parameters and histological changes after administration with MPDAFe@DOX@Mem NPs and PTT were observed in the kidneys, showing more pronounced changes than the liver, indicating potential kidney toxicity. Our research provides insights into oxidative stress and possible toxic effects after in vivo administration of mesoporous PDA NPs combined with chemotherapy-photothermal therapy (CT-PTT), which is extremely important for their future applications in anticancer therapies.

Mesoporous polydopamine (MPDA)-based drug delivery system for oral chemo-photothermal combinational therapy of orthotopic colon cancer

Oral nano-drug delivery systems offering combination therapy have garnered significant interest in colon cancer treatment due to their precision in targeting tumors and minimizing peripheral tissue exposure. However, challenges such as the complex gastrointestinal environment and effective retention of nanoparticles in the colon have impeded further advancement. We developed a novel oral drug delivery system designed for localized treatment of colon cancer via chemotherapy and photothermal therapy (PTT). This system utilized mesoporous polydopamine (MPDA) as a photothermal carrier for doxorubicin hydrochloride (DOX), with surface modification using folic acid (FA) to enhance systemic tumor targeting. Additionally, to ensure gastrointestinal retention and precise colon localization, the nanoparticles were coated with an enteric-soluble material, ES100, resulting in the formulation MPDA-FA-DOX/ES100. This formulation exhibited high photothermal conversion efficiency, robust photothermal stability, and responsive drug release under near-infrared (NIR) laser stimulation. FA modification significantly enhanced the cellular uptake of nanoparticles by CT26 cells, promoting greater cytotoxic effects through combined chemotherapy and PTT. In vivo, MPDA-FA-DOX/ES100 demonstrated superior accumulation in colon tumor tissues and substantial photothermal effects, and notably, the CT/PTT group demonstrated significant tumor growth inhibition along with excellent biocompatibility. Collectively, these findings highlight the clinical potential of MPDA-FA-DOX/ES100 as an effective platform for localized and synergistic CT/PTT of colon cancer.

Improving broadband absorption of carbon dot conjugated melanin via pre-doping strategy as interfacial photothermal evaporator

Photothermal seawater desalination harnesses solar energy to induce heat and expediates seawater evaporation and purification. The desalination efficacy heavily relies on the light absorption capability and microstructure of the solar evaporator. Polydopamine (PDA) represents a typical synthetic melanin with broad spectral absorption characteristics. However, its absorption capacity within the near-infrared (NIR) region is limited, leading to inadequate photothermal conversion efficiency. To overcome this challenge, we adopt a straightforward approach involving the pre-doping of N,S-doped carbon quantum dots (N,S-CQDs) with dopamine through covalent interaction to fabricate CQDs-loaded mesoporous polydopamine (MPDA-8). This strategy effectively reduces the band gap of PDA by fostering additional donor–acceptor pairs and π-stacking structures, thereby broadening the absorption capacity across the UV–Vis-NIR spectrum through nonradiative transitions. The MPDA-8 coated Balsa wood and cellulose evaporator achieved high evaporation rates of 1.82 kg m−2 h−1 and 2.10 kg m−2 h−1, respectively, overcoming the limit of 2D interfacial evaporator. The small pores and fiber channels within the wood, coupled with the hydrophilicity of MPDA-8, facilitates efficient water transportation and reduces evaporation enthalpy. Outdoor evaporation experiments conducted under sunlight corroborated the practical viability of this material. This study introduces a new perspective for advancing synthetic melanins in photothermal applications through the nanoparticle pre-doping strategy.

Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.

Mechanistic Insights into the Removal of Surfactant-Like Contaminants on Mesoporous Polydopamine Nanospheres from Complex Wastewater Matrices.

The detrimental environmental effects of surfactant-like contaminants (SLCs) with distinctive amphiphilic structures have garnered significant attention, particularly since perfluorooctanesulfonate was classified as a persistent organic pollutant. Despite the numerous absorbents developed for SLCs removal, the underlying interaction mechanisms remain speculative and lack experimental validation. To address this research gap, we elucidate the mechanistic insights into the selective removal of SLCs using mesoporous polydopamine nanospheres (MPDA) fabricated via a novel soft-template method. We employed low-field nuclear magnetic resonance to quantitatively characterize the hydrophilicity of the absorbents using water molecules as probes. The results demonstrated that MPDA with uniform mesopores exhibited a remarkable threefold enhancement in SLCs' adsorption capacity compared to conventional polydopamine particles via intraparticle diffusion. We further demonstrated the dominant effects of electrostatic and hydrophobic interactions on the selective removal of SLCs with MPDA by regulating the isoelectric pH value and performing a comparative analysis. The mechanism-inspired SLC-removal strategy achieved an average removal rate of 76.3% from highly contaminated wastewater. Our findings offer new avenues for applying MPDA as an efficient adsorbent and provide innovative and mechanistic insights for targeted SLC removal in complex wastewater matrices.

Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis.

In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.

Hyaluronic acid methacrylate/Pluronic F127 hydrogel enhanced with spermidine-modified mesoporous polydopamine nanoparticles for efficient synergistic periodontitis treatment

Bacterial infection, reactive oxygen species (ROS) accumulation, and persistent inflammation pose significant challenges in the treatment of periodontitis. However, the current single-modal strategy makes achieving the best treatment effect difficult. Herein, we developed a double-network hydrogel composed of Pluronic F127 (PF-127) and hyaluronic acid methacrylate (HAMA) loaded with spermidine-modified mesoporous polydopamine nanoparticles (M@S NPs). The PF-127/HAMA/M@S (PH/M@S) hydrogel was injectable and exhibited thermosensitivity and photocrosslinking capabilities, which enable it to adapt to the irregular shape of periodontal pockets. In vitro, the PH/M@S displayed multiple therapeutic effects, such as photothermal antibacterial activity, a high ROS scavenging capacity, and anti-inflammatory effects, which are beneficial for the multimodal treatment of periodontitis. The underlying anti-inflammatory mechanism of this hydrogel involves suppression of the extracellular regulated protein kinase 1/2 and nuclear factor kappa-B signalling pathways. Furthermore, in lipopolysaccharide-stimulated macrophage conditioned media, the PH/M@S effectively restored the osteogenic differentiation potential. In a rat model of periodontitis, the PH/M@S effectively reduced the bacterial load, relieved local inflammation and inhibited alveolar bone resorption. Collectively, these findings highlight the versatile functions of the PH/M@S, including photothermal antibacterial activity, ROS scavenging, and anti-inflammatory effects, indicating that this hydrogel is a promising multifunctional filling material for the treatment of periodontitis.

Construction of oxime functionalized mesoporous polydopamine spheres based on emulsion-induced interface assembly approach for efficient extraction of uranium

Highly efficient adsorption of uranium is of great concern in environmental protection and energy development. The oxime functionalized adsorbents are a promising approach for uranium adsorption owing to their relatively high specificity and affinity between the oxime group and uranium. Here, a porous oxime functionalized polydopamine microspheres (mPDA-oxime) were prepared through an emulsion-induced interface assembly approach based on amphiphilic F127 as the organic template agent, 1,3,5-trimethyl benzene (TMB) as the pore swelling, dopamine (DA) and salicylaldoxime (SAA) as carbon source. In this process, DA polymerization and fusion TMB/F127/DA, and simultaneous deposition of SAA were conducted to form PDA/SAA/F127/TMB microspheres under alkaline conditions. After removing TMB and F127, the mPDA-oxime sphere was obtained. The mPDA-oxime sphere exhibited superiorities in selectivity, kinetics, adsorption capacity, and reproducibility of uranium adsorption, which is an economically viable and industrially scalable realistic uranium extraction material. The design and fabrication of mPDA-oxime sphere makes the adsorbent extend the potential application in various fields.

Anti-oxidative mesoporous polydopamine-based hypotensive nano-eyedrop for improved glaucoma management

Conventional hypotensive eye drops remain suboptimal for glaucoma management, primarily due to their limited intraocular bioavailability and the growing concern regarding ocular surface side effects. Therefore, there is an urgent need to develop innovative intraocular pressure (IOP)-lowering formulations that not only possess enhanced corneal penetration ability but also provide ocular surface protection. Herein, anti-oxidative mesoporous polydopamine nanoparticles (MPDA NPs) were explored as a nano-carrier for Brimonidine to address the above issues. Nearly monodisperse MPDA NPs with obvious nanopores were successfully prepared by template-removal method and used for encapsulation of Brimonidine benefiting from their high specific surface area. Interestingly, the PEGylated and drug loaded MPDA-PEG@Brim NPs showed a near neutral surface charge, which is expected to enhance intraocular drug delivery. Consequently, much higher concentration of Brimonidine in the aqueous humor was found after topical administration of MPDA-PEG@Brim nano-dispersion as compared to free Brimonidine solution. Accordingly, superior IOP reduction effect was achieved for the nano-formulation in both hypertensive and normotensive rat eyes. Moreover, MPDA-PEG NPs showed good capability in scavenging diverse free radicals, alleviating intracellular oxidative stress, and mitigating ocular surface oxidative level in a mouse model of preservative-induced dry eye. In addition, the excellent biosafety of this novel Brimonidine nanodrug was confirmed both in vitro and in vivo. Therefore, the present work may shed light on the development of next generation hypotensive formulations for extended ocular surface protection and glaucoma management.

Silk-based nanocomposite hydrogel balances immune homeostasis via targeting mitochondria for diabetic wound healing

Patients with diabetes frequently experience impaired wound healing, a challenge commonly attributed to immune imbalance and oxidative stress; notably, these issues arise from mitochondrial dysfunction. In this study, we fabricate a naturally derived bioactive hydrogel by incorporating resveratrol-loaded mesoporous polydopamine nanoparticles into silk microfibers-reinforced methacrylated silk network (SS/MPDA@RES), which exhibits appropriate injectability, light-curable performance and mechanical strength. It effectively scavenges excessive ROS to protect mitochondria, restore ATP production and remodel redox homeostasis. More importantly, it promotes mitochondrial biogenesis, respiratory capacity and oxidative phosphorylation via the AMPK/SIRT1/PGC-1α signaling axis, thereby reprogramming macrophages to the anti-inflammatory phenotype. In vivo, SS/MPDA@RES hydrogel promotes wound healing in diabetic rats by modulating immunity, inhibiting early inflammation, and accelerating angiogenesis and collagen deposition. Targeting mitochondria to regulate immune and redox homeostasis provides a novel avenue for the design of future tissue regeneration materials, with SS/MPDA@RES emerging as a potential treatment strategy for diabetic wounds.

Photothermal and host immune activated therapy of cutaneous tuberculosis using macrophage targeted mesoporous polydopamine nanoparticles

Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by Mycobacterium tuberculosis (Mtb) infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe2+ and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on “bio-orthogonal chemistry”, combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

Membrane-camouflaged biomimetic nanoplatform with arsenic complex for synergistic reinforcement of liver cancer therapy.

Aim: Arsenic has excellent anti-advanced liver cancer effects through a variety of pathways, but its severe systemic toxicity forces the need for a safe and effective delivery strategy.Methods: Based on the chelating metal ion properties of polydopamine (PDA), arsenic was immobilized on an organic carrier, and a M1-like macrophage cell membrane (MM)-camouflaged manganese-arsenic complex mesoporous polydopamine (MnAsOx@MP@M) nanoplatform was successfully constructed. MnAsOx@MP@M was evaluated at the cellular level for tumor inhibition and tumor localization, and in vivo for its anti-liver cancer effect in a Hepa1-6 tumor-bearing mouse model.Results: The nanoplatform targeted the tumor site through the natural homing property of MM, completely degraded and released drugs to kill tumor cells in an acidic environment, while playing an immunomodulatory role in promoting tumor-associated macrophages (TAMs) repolarization.Conclusion: MnAsOx@MP@M has synergistically enhanced the targeted therapeutics against liver cancer via nanotechnology and immunotherapy, and it is expected to become a safe and multifunctional treatment platform in clinical oncology.

The Bioactive Interface of Titanium Implant with Both Anti-Oxidative Stress and Immunomodulatory Properties for Enhancing Osseointegration under Diabetic Condition.

The poor implant-osseointegration under diabetic condition remains a challenge to be addressed urgently. Studies have confirmed that the diabetic pathological microenvironment is accompanied by excessive oxidative stress, imbalanced immune homeostasis, and persistent chronic inflammation, which seriously impairs the osteogenic process. Herein, a multifunctional bioactive interface with both anti-oxidative stress and immunomodulatory properties is constructed on titanium implants. Briefly, manganese dioxide nanosheets are coated onto mesoporous polydopamine nanoparticles loaded with carbon monoxide gas precursor, namely MnO2-CO@MPDA NPs, and then they are integrated on the titanium implant to obtain MCM-Ti. In the simulated diabetic microenvironment, under the action of MnO2 nanoenzymes, MCM-Ti can effectively eliminate intracellular reactive oxygen species while alleviating hypoxic state. Interestingly, the microenvironment mediates the responsive release of CO gas, which effectively drives macrophages toward M2 polarization, thereby ameliorating inflammatory response. The potential mechanism is that CO gas up-regulates the expression of heme oxygenase-1, further activating the Notch/Hes1/Stat3 signaling pathway. Furthermore, the conditioned medium derived from macrophages on MCM-Ti surface significantly enhances the osteogenic differentiation of BMSCs. In a type 2 diabetic rat model, MCM-Ti implant effectively alleviates the accompanying inflammation and enhances the osseointegration through the synergistic effects of resisting oxidative stress and remodeling immune homeostasis.

Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS

Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (i.e., from-M1-to-M2 repolarization). In a murine periodontitis model, locally administered Q@MPDA reduced the presence of inflammatory macrophages, and decreased the levels of inflammatory cytokines (IL-1β and TNF-α) and reactive oxygen species (ROS) in the periodontium. Consequently, it alleviated periodontitis symptoms, reduced alveolar bone loss, and promoted tissue repair. Furthermore, our study revealed that Q@MPDA could inhibit the glycolysis of inflammatory macrophages while enhancing oxidative phosphorylation (OXPHOS), facilitating the shift from M1 to M2 macrophage subtype. Our findings suggest that Q@MPDA is a promising treatment for periodontitis via immunometabolic rewiring.