Mesoporous Polydopamine Nanoparticles Research Articles

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.

A mesoporous theranostic platform for ultrasound and photoacoustic dual imaging-guided photothermal and enhanced starvation therapy for cancer

Tumor starvation therapy utilizing glucose oxidase (GOx), has gained traction due to its non-invasive and bio-safe attributes. However, its effectiveness is often hampered by severe hypoxia in the tumor microenvironment (TME), limiting GOx's catalytic activity. To address this issue, a multifunctional nanosystem based on mesoporous polydopamine nanoparticles (MPDA NPs) was developled to alleviate TME hypoxia. This nanosystem integrated GOx modification and oxygenated perfluoropentane (PFP) encapsulation to address hypoxia-related challenges in the TME. Under NIR laser irradiation, the MPDA NPs exhibit significant photothermal conversion efficacy, activating targeted tumor photothermal therapy (PTT), while also serving as proficient photoacoustic (PA) imaging agents. The ensuing temperature rise facilitates oxygen (O2) release and induces liquid-gas conversion of PFP, generating microbubbles for enhanced ultrasound (US) imaging signals. The supplied oxygen alleviates local hypoxia, thereby enhancing GOx-mediated endogenous glucose consumption for tumor starvation. Overall, the integration of ultrasound/photoacoustic dual imaging-guided PTT and starvation therapy within MPDA-GOx@PFP@O2 nanoparticles (MGPO NPs) presents a promising platform for enhancing the efficacay of tumor treatment by overcoming the complexities of the TME. Statement of significanceA multifunctional MPDA-based theranostic nanoagent was developed for US/PAI imaging-guided PTT and starvation therapy against tumor hypoxia by direct O2 delivery. The incorporation of oxygenated perfluoropentane (PFP) within the mesoporous structure of MGPO not only enables efficient US imaging but also helps in alleviating tumor hypoxia. Moreover, the strong near-infrared (NIR) absorption of MGPO NPs promote the generation of PFP microbubbles and release of oxygen, thereby enhancing US imaging and GOx-mediated starvation therapy. Such a multifunctional nanosystem leverages synergistic effects to enhance therapeutic efficacy while incorporating US/PA imaging for precise visualization of the tumor.

Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO2 and coated with platelet membrane provide synergistic anti-tumor therapy

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 μg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.

Curcumin-loaded mesoporous polydopamine nanoparticles modified by quaternized chitosan against bacterial infection through synergistic effect

Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 μg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm2). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.

Multiple Treatment of Triple-Negative Breast Cancer Through Gambogic Acid-Loaded Mesoporous Polydopamine.

Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.

Investigating the Effectiveness of Different Porous Nanoparticles as Drug Carriers for Retaining the Photostability of Pinosylvin Derivative.

Pinosylvin monomethyl ether (PsMME) is a natural compound known for its valuable bioactive properties, including antioxidant and anti-inflammatory effects. However, PsMME's susceptibility to photodegradation upon exposure to ultraviolet (UV) radiation poses a significant limitation to its applications in the pharmaceutical field. This study, for the first time, introduces a strategy to enhance the photostability of PsMME by employing various nanoformulations. We utilized mesoporous silica nanoparticles (MSNs) coated with polydopamine via a poly(ethylene imine) layer (PDA-PEI-MSNs), thermally carbonized porous silicon nanoparticles (TCPSi), and pure mesoporous polydopamine nanoparticles (MPDA). All these nanocarriers exhibit unique characteristics, including the potential for shielding the drug from UV light, which makes them promising for enhancing the photostability of loaded drugs. Here, these three nanoparticles were synthesized and their morphological and physicochemical properties, including size and ζ-potential, were characterized. They were subsequently loaded with PsMME, and the release profiles and kinetics of all three nanoformulations were determined. To assess their photoprotection ability, we employed gas chromatography with a flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS) to assess the recovery percentage of loaded PsMME before and after UV exposure for each nanoformulation. Our findings reveal that MPDA exhibits the highest protection ability, with a remarkable 90% protection against UV light on average. This positions MPDA as an ideal carrier for PsMME, and by extension, potentially for other photolabile drugs as well. As a final confirmation of its suitability as a drug nanocarrier, we conducted cytotoxicity evaluations of PsMME-loaded MPDA, demonstrating dose-dependent drug toxicity for this formulation.

Synergistic Chemo-Photothermal Therapy of Breast Cancer Based on Mesoporous Polydopamine Nanoparticles Decorated with Atovaquone

Synergistic Chemo-Photothermal Therapy of Breast Cancer Based on Mesoporous Polydopamine Nanoparticles Decorated with Atovaquone

Multidimensional response of dopamine nano-system for on-demand fungicides delivery: Reduced toxicity and synergistic antibacterial effects

Considering the microenvironment of pathogens, the use of highly biocompatible antibacterial materials loaded with fungicides and the on-demand delivery of fungicides through controlled release can effectively improve the biocompatibility and antibacterial effect of existing fungicides. In this study, we used mesoporous poly-dopamine nanoparticles (MPDA NPs) as a carrier, prochloraz (Pro) as a loading agent, and benzimidazole (BIZ) and β-cyclodextrin (β-CD) complex as a blocking agent to prepare the on-demand delivery nano-pesticides Pro@MPDA-BIZ@β-CD (hereinafter abbreviated as PMBD), which can be administered at different stages. Sclerotinia sclerotiorum secretes oxalic acid factor to create an acidic microenvironment, and the nano-system quickly releases fungicide Pro into the mycelium. MPDA materials also responds to oxalic acid to jointly reduce the pathogenicity of Sclerotinia sclerotiorum, effectively inhibiting the growth of Sclerotinia sclerotiorum, and realizing the treatment of Sclerotinia sclerotiorum infection. On the other hand, when plants are not infected with Sclerotinia sclerotiorum, MPDA with a photothermal effect triggers the release of fungicides under the irradiation of near-infrared light, thus preventing Sclerotinia sclerotiorum infection. The in vitro release experiment showed that the cumulative release of Pro under low pH and near-infrared light irradiation was 2.68 times and 2.04 times higher than that under neutral and no light conditions, respectively. On the other hand, the rich functional groups on MPDA-BIZ@β-CD(hereinafter abbreviated as MBD) gave the system good wettability, and the contact angles of MBD on Chinese cabbage and tomato leaves were reduced by 14.85° and 41.54°, respectively, which enhanced its resistance to rainwater erosion and prevented the fungicides from being lost to the environment. In addition, bio-safety experiments have shown that PMBD has good biocompatibility to plant germination and soil microorganisms.

PH-Responsive Sorafenib/Iron-Co-Loaded Mesoporous Polydopamine Nanoparticles for Synergistic Ferroptosis and Photothermal Therapy.

Ferroptosis has attracted significant attention as a new mechanism of cell death. Sorafenib (SRF) is widely considered a prototypical ferroptosis-inducing drug, particularly for liver cancer treatment. However, the low solubility and hydrophobic nature of SRF, along with the absence of synergistic therapeutic strategies, still limit its application in cancer treatment. Herein, we report a dual therapeutic method incorporating photothermal therapy and ferroptosis by using Fe-doped mesoporous polydopamine nanoparticles (Fe-mPDA@SRF-TPP) as a carrier for loading SRF and targeting triphenylphosphine (TPP). SRF molecules are efficiently encapsulated within the polydopamine nanospheres with a high loading ratio (80%) attributed to the porosity of Fe-mPDA, and the inherent biocompatibility and hydrophilicity of Fe-mPDA@SRF-TPP facilitate the transport of SRF to the target cancer cells. Under the external stimuli of acidic environment (pH 5.0), glutathione (GSH), and laser irradiation, Fe-mPDA@SRF-TPP shows sustained release of SRF and Fe ions with the ratio of 72 and 50% within 48 h. Fe-mPDA@SRF-TPP nanoparticles induce intracellular GSH depletion, inhibit glutathione peroxidase 4 (GPX4) activity, and generate hydroxyl radicals, all of which are essential components of the therapeutic ferroptosis process for killing MDA-MB-231 cancer cells. Additionally, the excellent near-infrared (NIR) light absorption of Fe-mPDA@SRF-TPP nanoparticles demonstrates their capability for photothermal therapy and further enhances the therapeutic efficiency. Therefore, this nanosystem provides a multifunctional therapeutic platform that overcomes the therapeutic limitations associated with standalone ferroptosis and enhances the therapeutic efficacy of SRF for breast cancer.

Biomimetic theranostic nanoparticles for effective anticancer therapy and MRI imaging

Cancer remains a leading cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Nanoparticle-based drug delivery systems have garnered significant interest due to their multifunctionality, offering the potential to enhance cancer treatment efficacy and improve patient tolerability. Membrane-coated drug delivery systems hold great potential for enhancing the therapeutic outcome of nanoparticle-based anticancer therapies. In this study, we report the synthesis of multifunctional iron-functionalized mesoporous polydopamine nanoparticles (MPDAFe NPs). These nanoformulations demonstrate substantial potential for combining efficient drug delivery and magnetic resonance imaging (MRI) and showcase the advantages of biomimetic coating with tumor cell-derived membranes. This coating confers prolonged circulation and improved the targeting capabilities of the nanoparticles. Furthermore, comprehensive biosafety evaluations reveal negligible toxicity to normal cells, while the combined chemo- and phototherapy exhibited significant cytotoxicity towards cancer cells. Additionally, the photothermal effect evaluation highlights the enhanced cytotoxicity achieved through laser irradiation, showcasing the synergistic effects of the nanomaterials and photothermal therapy. Importantly, our chemotherapeutic effect evaluation demonstrates the superior efficacy of doxorubicin-loaded MPDAFe@Mem NPs (cancer cell membrane-coated MPDAFe NPs) in inhibiting cancer cell viability and proliferation, surpassing the potency of free doxorubicin. This study comprehensively investigates theranostic, membrane-coated drug delivery systems, underlining their potential to increase the efficacy of cancer treatment strategies. The multifunctional nature of the iron-functionalized polydopamine nanoparticles allows for efficient drug delivery and imaging capabilities, while the biomimetic coating enhances their biocompatibility and targeting ability. These findings contribute valuable insights towards the development of advanced nanomedicine for improved cancer therapeutics.

An Orally-Administered Nanotherapeutics with Carbon Monoxide Supplying for Inflammatory Bowel Disease Therapy by Scavenging Oxidative Stress and Restoring Gut Immune Homeostasis.

Traditional drug-based treatments for inflammatory bowel disease (IBD) have significant limitations due to their potential off-target systemic side-effects. Currently, there is a lack of understanding on how to effectively address excessive oxidative stress, dysregulated immune homeostasis, and microbiota dysbiosis within the IBD microenvironment. Herein, we introduce a nanotherapeutic approach, named LBL-CO@MPDA, for IBD treatment. LBL-CO@MPDA is an orally administered formulation that supplies carbon monoxide (CO) for therapeutic purposes. To create the LBL-CO@MPDA nanocomposite, we developed a layer by layer (LBL) self-assembly strategy where we coated chitosan/alginate polyelectrolytes onto the surface of CO prodrug-loaded mesoporous polydopamine nanoparticles (CO@MPDA). Benefiting from the negatively charged surface of the LBL coating, it allows for targeted accumulation of LBL-CO@MPDA specifically onto the positively charged inflamed colon lesions through electrostatic interactions. Furthermore, in the oxidative microenvironment of the inflamed colon, the nanotherapeutic system releases CO in a responsive manner. Interestingly, CO@MPDA ameliorates inflammatory conditions by MPDA-mediated ROS-scavenging and CO-mediated immunomodulation. CO-supplying activates heme oxygenase-1, leading to macrophage M2 polarization via the Notch/Hes1/Stat3 signaling pathway, while suppressing the inflammatory response by down-regulating the p38 MAPK and NF-κB (p50/p65) signaling pathways. In the mice model of dextran sulfate sodium (DSS)-induced IBD, LBL-CO@MPDA effectively reverses the pro-inflammatory microenvironment and restores gut barrier functions through multiple mechanisms, including scavenging oxidative stress, restoring immune homeostasis, and modulating the gut microbiota. Collectively, our findings highlight the promising potential of this innovative nanotherapeutic strategy for the targeted treatment of IBD.

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

Mussel bioinspired, silver-coated and insulin-loaded mesoporous polydopamine nanoparticles reinforced hyaluronate-based fibrous hydrogel for potential diabetic wound healing

Diabetes wounds take longer to heal due to extended inflammation, decreased angiogenesis, bacterial infection, and oxidative stress. These factors underscore the need for biocompatible and multifunctional dressings with appropriate physicochemical and swelling properties to accelerate wound healing. Herein, insulin (Ins)-loaded, and silver (Ag) coated mesoporous polydopamine (mPD) nanoparticles were synthesized (Ag@Ins-mPD). The nanoparticles were dispersed into polycaprolactone/methacrylated hyaluronate aldehyde dispersion, electrospun to form nanofibers, and then photochemically crosslinked to form a fibrous hydrogel. The nanoparticle, fibrous hydrogel, and nanoparticle-reinforced fibrous hydrogel were characterized for their morphological, mechanical, physicochemical, swelling, drug-release, antibacterial, antioxidant, and cytocompatibility properties. The diabetic wound reconstruction potential of nanoparticle-reinforced fibrous hydrogel was studied using BALB/c mice. The results indicated that Ins-mPD acted as a reductant to synthesize Ag nanoparticles on their surface, held antibacterial and antioxidant potential, and their mesoporous properties are crucial for insulin loading and sustained release. The nanoparticle-reinforced scaffolds were uniform in architecture, porous, mechanically stable, showed good swelling, and possessed superior antibacterial, and cell-responsive properties. Furthermore, the designed fibrous hydrogel scaffold demonstrated good angiogenic, anti-inflammatory, increased collagen deposition, and faster wound repair capabilities, therefore, it could be used as a potential candidate for diabetic wound treatment.

Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a common autoimmune disease leading to pain, disability, and even death. Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases, the role of STING in RA remains unclear. In the current study, we demonstrated that STING activation was pivotal in RA pathogenesis. As the accumulation of dsDNA, a specific stimulus for STING, is a feature of RA, we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176 (PEI-PDA@C-176 NPs) for treating RA. The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages. Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway. We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA.

A Photo‐Therapeutic Nanocomposite with Bio‐Responsive Oxygen Self‐Supplying Combats Biofilm Infections and Inflammation from Drug‐Resistant Bacteria

AbstractThe use of non‐antibiotic strategies to combat refractory drug‐resistant bacterial infections, especially biofilms and accompanying inflammation, has recently aroused widespread interest. Herein, a photo‐therapeutic nanocomposite with bio‐responsive oxygen (O2) self‐supplying is introduced by integrating manganese dioxide (MnO2) nanozymes onto photosensitizer (indocyanine green, ICG)‐loaded mesoporous polydopamine nanoparticles (MPDA), namely MI‐MPDA NPs. MI‐MPDA can activate O2 generation in the infection microenvironment, thereby effectively alleviating biofilm hypoxia. Under near‐infrared light (NIR) irradiation, continuous O2 supplying further boosts the level of singlet oxygen (1O2), enabling robust biofilm elimination through O2‐potentiated photodynamic/photothermal therapy. Interestingly, MI‐MPDA down‐regulates the factor expression of inflammatory signaling pathways through MnO2‐mediated reactive oxygen species scavenging, which ameliorates the inflammatory condition. Meanwhile, O2 supplying prevents the M1‐phenotype switch of macrophages from the overexpression of hypoxia‐inducible factor‐1α (HIF‐1α), thereby prompting macrophage reprogramming toward pro‐regenerative M2‐phenotype. In the mouse models of subcutaneous implant‐associated infection caused by methicillin‐resistant Staphylococcus aureus (MRSA) biofilms and burn infection caused by Pseudomonas aeruginosa biofilms, NIR‐irradiated MI‐MPDA not only effectively eliminates the formed biofilms, but also alleviates the oxidative stress and accompanying inflammation, and drives the cascade reaction of immunomodulation‐wound healing. Overall, this O2‐potentiated photo‐therapeutic strategy provides a reliable tool for combating biofilm infections and inflammation from drug‐resistant bacteria.

Multifunctional mesoporous polydopamine near-infrared photothermal controlled release of kartogenin for cartilage repair

Improving chondrogenic differentiation while inhibiting hypertrophic differentiation of mesenchymal stem cells (MSCs) is of vital importance to effectively repairing cartilage injury. Accordingly, kartogenin (KGN) and antioxidants, which promote chondrogenic differentiation and inhibit hypertrophic differentiation, respectively, have shown great potential in promoting cartilage repair. However, KGN is poorly soluble in water, hindering efficient intracellular delivery. Near-infrared light (NIR)-responsive mesoporous polydopamine nanoparticles (MPDA) reportedly exert antioxidative effects by eliminating reactive oxygen species (ROS). In this study, we assessed whether KGN loaded in MPDA can accelerate cartilage injury repair in rats. Specifically, a thermosensitive phase-change material (PCM, melting point 39 °C) combined with KGN was loaded into MPDA as a gatekeeper (KGN@MPDA-PCM). The results showed that KGN@MPDA-PCM exhibited excellent photothermal properties under NIR irradiation, which induced PCM melting and consequent KGN release. In combination with antioxidative therapy, NIR-triggered KGN release enabled the nanocomposite to accelerate MSC chondrogenic differentiation and inhibit hypertrophic differentiation. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the rat model. RNA sequencing found that this MPDA-based platform promotes chondrogenic differentiation by promoting fibronectin-1 (Fn1) expression and activating the PI3K/Akt pathway. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for accelerating cartilage injury repair.

Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery

BackgroundThere are few effective medications for treating colorectal cancer and liver metastases (CRLM). The interactions among glycolysis, epithelial-mesenchymal transition (EMT), and immune microenvironment contribute to the progression of CRLM. A main glycolytic enzyme pyruvate Kinase M2 (PKM2) is highly expressed in colorectal cancer and CRLM, and thus can be a potential therapeutic target.MethodsA therapeutic strategy was proposed and the shikonin-loaded and hyaluronic acid-modified MPDA nanoparticles (SHK@HA-MPDA) were designed for CRLM therapy via PKM2 inhibition for immunometabolic reprogramming. The treatment efficacy was evaluated in various murine models with liver metastasis of colorectal tumor.ResultsSHK@HA-MPDA achieved tumor-targeted delivery via hyaluronic acid-mediated binding with the tumor-associated CD44, and efficiently arrested colorectal tumor growth. The inhibition of PKM2 by SHK@HA-MPDA led to the remodeling of the tumor immune microenvironment and reversing EMT by lactate abatement and the suppression of TGFβ signaling; the amount of cytotoxic effector CD8+ T cells was increased while the immunosuppressive MDSCs decreased.ConclusionThe work provided a promising targeted delivery strategy for CRLM treatment by regulating glycolysis, EMT, and anticancer immunity.Graphic abstractAn immunometabolic strategy for treating colorectal cancer liver metastases using the shikonin-loaded, hyaluronic acid-modified mesoporous polydopamine nanoparticles (SHK@HA-MPDA) via glycolysis inhibition, anticancer immunity activation, and EMT reversal. SHK@HA-MPDA can inhibit cytoplasmic PKM2 and glycolysis of the tumor and reduce lactate flux, and then activate the DCs and remodel the tumor immune microenvironment. The reduced lactate flux can reduce MDSC migration and suppress EMT.

Microneedle patches containing mesoporous polydopamine nanoparticles loaded with triamcinolone acetonide for the treatment of oral mucositis.

Oral mucositis (OM) is the most common disease of the oral mucosa, which affects people's daily production and life. Triamcinolone ointment is the common clinical drug for OM treatment. However, the hydrophobic properties of triamcinolone acetonide (TA) and the complex microenvironment of the oral cavity led to its low bioavailability and unstable therapeutic effects on ulcer wounds. Herein, dissolving microneedle patches (MNs) composed of mesoporous polydopamine nanoparticles (MPDA) loaded with TA (TA@MPDA), sodium hyaluronic acid (HA), and Bletilla striata polysaccharide (BSP) are prepared as the transmucosal delivery system. The prepared TA@MPDA-HA/BSP MNs exhibit well-arranged microarrays, high mechanical strength and fast solubility (<3min) properties. In addition, the hybrid structure improves the biocompatibility of TA@MPDA and expedites oral ulcer healing in the SD rat model through the synergistic anti-inflammatory and pro-healing effects of microneedle ingredients (hormones, MPDA and Chinese herbs extracts), with 90% less amount of TA compared with Ning Zhi Zhu®. TA@MPDA-HA/BSP MNs are shown to be their great potential as novel ulcer dressings for OM management.