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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-1 β 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. Q@MPDA via metabolic regulation reprograms inflammatory macrophages to anti-inflammatory, reduces pro-inflammation cytokines and ROS, alleviates periodontitis, and promotes tissue repair. [Display omitted] [ABSTRACT FROM AUTHOR]

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. Article highlights Small inorganic molecules drug was assembled on an organic carrier. Arsenic was combined with metallic hydroxyl (Mn-OH) groups by adsorption to form a monodentate compound. The metal ion chelating property of polydopamine was utilized to load manganese. The mesoporous structure of polydopamine was favorable for loading more metal ions. polydopamine was completely degraded in an acidic environment, and the product dopamine could regulate tumor vascular homeostasis. The camouflage of the macrophage cell membrane helped the nano-drug delivery system evade immune surveillance, prolong circulation time in the body and enrich the tumor. The tumor sphere experiment preliminarily confirmed that the enhanced tumor permeability of the preparation was based on macrophage cell membrane. M1 macrophage membrane helped regulate the TAMs immune promotion. [ABSTRACT FROM AUTHOR]

Xiaochen Ma,1 Yubo Cui,2 Min Zhang,1 Qinghua Lyu,2 Jun Zhao2 1The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, People’s Republic of China; 2Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Qinghua Lyu; Jun Zhao, Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, People’s Republic of China, Email a0129473@u.nus.edu; doctorzhaojun@163.comIntroduction: Oxidant stress, abnormal angiogenesis, and inflammation are three key factors contributing to the development of ocular neovascular diseases (ONDs). This study aims to develop a multifunctional nanodrug, DEX@MPDA-Arg@Si (DMAS), which integrates mesoporous polydopamine, vascular endothelial growth factor (VEGF)-siRNA, and dexamethasone (DEX) to address these therapeutic targets.Methods: Physicochemical properties of DMAS were measured using transmission electron microscopy and a nanoparticle size analyzer. The encapsulation efficiency and drug loading capacity of DMAS were measured using a UV-visible spectrophotometer. The in vivo therapeutic efficacy and ocular safety of DMAS were evaluated using three established mouse models, including the alkali burn-induced corneal neovascularization (CoNV) model, the oxygen-induced retinopathy (OIR) model, and the laser-induced choroidal neovascularization (CNV) model.Results: The DMAS nanoparticles demonstrated a uniform bowl-like shape with an average size of 264.9 ± 2.5 nm and a zeta potential of − 28.2 ± 4.2 mV. They exhibited high drug-loading efficiency (36.04 ± 3.60% for DEX) and excellent biocompatibility. In vitro studies confirmed its potent antioxidant, anti-inflammatory, and anti-apoptotic properties. In vivo, DMAS treatment led to significant therapeutic effects across all models. It effectively inhibited CoNV, promoted corneal repair, and modulated inflammation in the alkali burn model. In the OIR model, DMAS reduced retinal neovascularization by decreasing VEGF expression. In the laser-induced CNV model, it significantly reduced the CNV area and lesion thickness.Conclusion: This research developed a multifunctional nanodrug, DMAS, capable of co-delivering VEGF-siRNA and DEX, offering synergistic therapeutic benefits for treating ONDs. The DMAS nanodrug demonstrates promising anti-inflammatory, antioxidative, and anti-angiogenic effects, highlighting its potential as a versatile and effective treatment for multiple ocular conditions.Keywords: mesoporous polydopamine, nano-delivery platform, ocular neovascular diseases, dexamethasone, VEGF-siRNA

Yang Liu,1,* Chunan Wang,1,* Sitong Liu,1,* Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email caozhong@mail.sysu.edu.cn; wjinm@mail.sysu.edu.cnBackground: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy

Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio‐based hydrogel microspheres 'micro‐cage', termed mPDA‐PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique 'micro‐cage' construct is designed to non‐contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into 'micro‐cage' along with wound exudation, and cationic mPDA‐PEI immobilizes them inside the 'micro‐cage' through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non‐contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications. [ABSTRACT FROM AUTHOR]

CO gas therapy has attracted enormous attention in tumor therapy due to the abilities of mitochondrial damage and inhibition of cellular respiration. However, the inefficient and random release of CO greatly limit its application. Taking this into account, the study constructs an acid‐unlocked nanostructure based on MPDA‐MnCO‐GOx@DSNPs, designated as MMGD. The nanostructure enables tumor microenvironment (TME) specific enzyme and CO prodrug (manganese carbonyl, MnCO) cascade reaction, thus facilitating CO release in situ. Mesoporous polydopamine (MPDA) can provide the space for MnCO and glucose oxidase (GOx) loading. Especially, lanthanide (Ln3+)‐doped down‐shifting luminescent nanoparticles (DSNPs) can not only serve as the near‐infrared II (NIR‐II) fluorescence imaging probe, but also act as the acid‐unlocked gating switch. The slightly acidic TME can render the dissociation of DSNPs, thus exposing GOx and releasing MnCO. The catalytic reaction of GOx can produce H2O2 and create a more acidic environment, which facilitates the CO generation in situ, leading to mitochondrial damage by reducing cytochrome c oxidase activity and adenosine triphosphate (ATP) levels. Meanwhile, MPDA has the NIR light absorption capability for photothermal therapy (PTT). This study provides an ingenious strategy for efficient and controllable CO gas, starvation, and PTT of tumor guided by NIR‐II fluorescence imaging. [ABSTRACT FROM AUTHOR]

The rapid emergence and spread of drug-resistant pathogens pose a serious threat to human health. To overcome this problem, the exploration of new antibacterial agents, especially antibiotic-free strategies, is urgent. Here, nitric oxide (NO) release and photothermal effects were integrated into a single nanoplatform to achieve more efficient antibacterial effects. The nanoplatform (SNP/MPDA) was composed of mesoporous polydopamine (MPDA) and sodium nitroferricyanide (III) dihydrate (SNP). Near-infrared (NIR)-light could make MPDA produce high temperature, which could not only effectively kill bacteria but also induce SNPs to generate NO to kill bacteria. The NO/photothermal strategy showed the ability to kill both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and destruct mature biofilm. This antibiotic-free strategy had the advantage of producing NO in situ, thereby showing its high antibacterial activity and great potential in killing pathogens. This work provides insights into the design of more efficient antimicrobial strategies without antibiotics. [ABSTRACT FROM AUTHOR]

It remains challenging to develop an effective therapeutic agent for breast cancer. Synergistic therapies, particularly chemo-photothermal therapy, have gained increasing attention in cancer treatment. While the high working temperature achieved in photothermal therapy can kill tumor cells, it also causes thermal damage to nearby healthy cells, limiting the clinical application of chemo-photothermal synergistic therapy. To address these limitations, we have successfully synthesized nanoparticles by combining mesoporous polydopamine with atovaquone (ATO), denoted MPDA-ATO. These nanoparticles (NPs) enable chemo-photothermal therapy to be conducted at a mildly increased temperature of 46 °C. The MPDA-ATO NPs exhibit excellent photothermal stability, potent photothermal conversion properties, and good biocompatibility. In response to near-infrared radiation (NIR), MPDA-ATO can effectively kill 4T1 breast tumor cells in vitro and in the synergistic host. Furthermore, the MPDA-ATO NPs specifically inhibit STAT3, contributing to the antitumor effect. The treatment combining MPDA-ATO NPs with NIR could induce the apoptosis of tumor cells. In summary, the MPDA-ATO NPs offer improved efficacy and safety in treating breast cancer, providing insights and strategies for improved breast cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio‐based hydrogel microspheres ‘micro‐cage’, termed mPDA‐PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique ‘micro‐cage’ construct is designed to non‐contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into ‘micro‐cage’ along with wound exudation, and cationic mPDA‐PEI immobilizes them inside the ‘micro‐cage’ through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non‐contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

Abstract Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.

Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T 1 intensity. In comparison, the rare element Holmium (Ho)-based nanoparticles (NPs) have demonstrated great potential as T 2 -weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (∼ 10−13s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III)-doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug-loading capability and great potential as Ho (III)-based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near-infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor-targeting chemo-photothermal therapy against 4T1 breast cancer. Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T 1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T 2 MRI properties (r 2 = 152.13 mM−1s−1) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform. [ABSTRACT FROM AUTHOR]

Abstract In the treatment of spinal cord injury (SCI), the complex process of secondary injury is mainly responsible for preventing SCI repair or even exacerbating the injury. In this experiment, we constructed the 8-gingerol (8G)-loaded mesoporous polydopamine (M-PDA), M@8G, as the in vivo targeting nano-delivery platform, and investigated the therapeutic effects of M@8G in secondary SCI and its related mechanisms. The results indicated that M@8G could penetrate the blood-spinal cord barrier to enrich the spinal cord injury site. Mechanism research has shown that all of the M-PDA,8G and M@8G displayed the anti-lipid peroxidation effect, and then M@8G can inhibit the secondary SCI by suppressing the ferroptosis and inflammation. In vivo assays showed that M@8G significantly diminished the local injury area, reduced axonal and myelin loss, thus improving the neurological and motor recovery in rats. Based on the analysis of cerebrospinal fluid samples from patients, ferroptosis occurred locally in SCI and continued to progress in patients during the acute phase of SCI as well as the stage after their clinical surgery. This study showcases effective treatment of SCI through the aggregation and synergistic effect of M@8G in focal areas, providing a safe and promising strategy for the clinical treatment of SCI.

Abstract Hypoxia and high accumulation of lactic acid in the tumor microenvironment provide fertile soil for tumor development, maintenance and metastasis. Herein, we developed a calcium peroxide (CaO2)-loaded nanostructure that can play a role of “one stone kill two birds”, i.e., acidic and hypoxic tumor microenvironment can be simultaneously regulated by CaO2 loaded nanostructure. Specifically, CaO2-loaded mesoporous polydopamine nanoparticles modified with sodium hyaluronate (denoted as CaO2@mPDA-SH) can gradually accumulate in a tumor site. CaO2 exposed in acidic microenvironment can succeed in consuming the lactic acid with oxygen generation simultaneously, which could remodel the acid and hypoxia tumor microenvironment. More importantly, the relief of hypoxia could further reduce lactate production from the source by down-regulating the hypoxia inducible factor-1α (HIF-1α), which further down-regulated the glycolysis associated enzymes including glycolysis-related glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). As a result, CaO2@mPDA-SH alone without the employment of other therapeutics can dually regulate the tumor hypoxia and lactic acid metabolism, which efficiently represses tumor progression in promoting immune activation, antitumor metastasis, and anti-angiogenesis.

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd3+/DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd3+/DOX had a high photothermal conversion efficiency of 33.4% and excellent T1−MRI performance with a longitudinal relaxivity (r1) value of 14.966 mM−1·s − 1. Moreover, the results suggested that FMPDA/Gd3+/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd3+/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd3+/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics

In the treatment of spinal cord injury (SCI), the complex process of secondary injury is mainly responsible for preventing SCI repair or even exacerbating the injury. In this experiment, we constructed the 8-gingerol (8G)-loaded mesoporous polydopamine (M-PDA), M@8G, as the in vivo targeting nano-delivery platform, and investigated the therapeutic effects of M@8G in secondary SCI and its related mechanisms. The results indicated that M@8G could penetrate the blood-spinal cord barrier to enrich the spinal cord injury site. Mechanism research has shown that all of the M-PDA,8G and M@8G displayed the anti-lipid peroxidation effect, and then M@8G can inhibit the secondary SCI by suppressing the ferroptosis and inflammation. In vivo assays showed that M@8G significantly diminished the local injury area, reduced axonal and myelin loss, thus improving the neurological and motor recovery in rats. Based on the analysis of cerebrospinal fluid samples from patients, ferroptosis occurred locally in SCI and continued to progress in patients during the acute phase of SCI as well as the stage after their clinical surgery. This study showcases effective treatment of SCI through the aggregation and synergistic effect of M@8G in focal areas, providing a safe and promising strategy for the clinical treatment of SCI. [ABSTRACT FROM AUTHOR]

The treatments generally employed for temporomandibular joint osteoarthritis (TMJOA) involve physical therapy and chemotherapy, etc., whose therapeutic efficacies are impaired by the side effects and suboptimal stimulus responsiveness. Although the intra-articular drug delivery system (DDS) has shown effectiveness in addressing osteoarthritis, there is currently little reported research regarding the use of stimuli-responsive DDS in managing TMJOA. Herein, we prepared a novel near-infrared (NIR) light-sensitive DDS (DS-TD/MPDA) by using mesoporous polydopamine nanospheres (MPDA) as NIR responders and drug carriers; diclofenac sodium (DS) as the anti-inflammatory medication; and 1-tetradecanol (TD) with a phase-inversion temperature of 39 °C as the drug administrator. Upon exposure to 808 nm NIR laser, DS-TD/MPDA could raise the temperature up to the melting point of TD through photothermal conversion, and intelligently trigger DS release. The resultant nanospheres exhibited an excellent photothermal effect and effectively controlled the release of DS through laser irradiation to accommodate the multifunctional therapeutic effect. More importantly, the biological evaluation of DS-TD/MPDA for TMJOA treatment was also performed for the first time. The experiments' results demonstrated that DS-TD/MPDA displayed a good biocompatibility in vitro and in vivo during metabolism. After injection into the TMJ of rats afflicted with TMJOA induced by unilateral anterior crossbite for 14 days, DS-TD/MPDA could alleviate the deterioration of TMJ cartilage, thus ameliorating osteoarthritis. Therefore, DS-TD/MPDA could be a promising candidate for photothermal-chemotherapy for TMJOA. [ABSTRACT FROM AUTHOR]

Current treatments for infections caused by multidrug‐resistant bacteria still remain challenging and therapeutic materials with high efficacy are of demand. Herein, a bactericidal nanocomposite was constructed by loading Roxarsone (ROX) onto nitrosylated mesoporous polydopamine (named mPDA@NO‐ROX). The designed nanocomposite exhibited considerable photothermal effect and controlled NO and ROX co‐delivery under the irradiation of near‐infrared laser (NIR) to achieve enhanced chemo‐photothermal antibacterial therapy. The in vitro antibacterial evaluation of the mPDA@NO‐ROX demonstrated the effective elimination of the Gram‐negative tetracycline‐resistant Escherichia coil and Gram‐positive methicillin‐resistant Staphylococcus aureus under mild NIR irradiation compared to merely ROX loaded unmodified mPDA, indicating the NO enhanced chemo‐photothermal therapy. In addition, the cytotoxicity experiments indicated that mPDA@NO‐ROX exhibited only 5 % of hemolysis rate and high cell viability at 1 mg mL−1 against mammalian fibroblasts, suggesting the excellent biocompatibility. In conclusion, the mPDA@NO‐ROX could be a promising candidate for anti‐infection therapy of multidrug‐resistant bacteria. [ABSTRACT FROM AUTHOR]

In clinical cancer research, photothermal therapy is one of the most effective ways to increase sensitivity to chemotherapy. Here, we present a simple and effective method for developing a nanotherapeutic agent for chemotherapy combined with photothermal therapy. The nanotherapeutic agent mesoporous polydopamine-Fe(III)-doxorubicin-hyaluronic acid (MPDA-Fe(III)-DOX-HA) was composed of mesoporous polydopamine modified by ferric ions and loaded with the anticancer drug doxorubicin (DOX), as well as an outer layer coating of hyaluronic acid. The pore size of the mesoporous polydopamine was larger than that of the common polydopamine nanoparticles, and the particle size of MPDA-Fe(III)-DOX-HA nanoparticles was 179 ± 19 nm. With the presence of ferric ions, the heat generation effect of the MPDA-Fe(III)-DOX-HA nanoparticles in the near-infrared light at 808 nm was enhanced. In addition, the experimental findings revealed that the active targeting of hyaluronic acid to tumor cells mitigated the toxicity of DOX on normal cells. Furthermore, under 808 nm illumination, the MPDA-Fe(III)-DOX-HA nanoparticles demonstrated potent cytotoxicity to HCT-116 cells, indicating a good anti-tumor effect in vitro. Therefore, the system developed in this work merits further investigation as a potential nanotherapeutic platform for photothermal treatment of cancer. [ABSTRACT FROM AUTHOR]

Osteosarcoma, occurring most frequently in adolescents, are highly malignant bone tumor and prone to develop local recurrence and long-distance metastasis. Therefore, new comprehensive therapeutic strategies for osteosarcoma are urgently needed. Different from traditional photothermal therapy (PTT), low temperature PTT (LTPTT) not only brings less heat damages to the surrounding normal tissues but also prevent tumor metastasis. Nevertheless, its therapeutic effects are severely attenuated due to the tumor thermo-resistance induced by the overexpression of heat shock protein (HSP). In our work, an acid-responsive core–shell nanocomposite was fabricated for cancer therapy. The nanoplatform can independently encapsulate alkyl radical initiator 2,2-azobis[2-(2-imidazolin-2-yl) propane]-dihydroch-loride (AIPH) in the mesoporous polydopamine (MPDA) core and HSP inhibitor (gambogic acid, GA) in the zeolite imidazolate framework-8 (ZIF-8) microporous shell, called MPDA/AIPH@ZIF-8/GA (MAZG), which could achieve the combined functions of LTPTT and thermodynamic therapy (TDT). After endocytosing by tumor cells, the pH-responsive degradation of the ZIF-8 coating stimulates the rapid release of GA, which can effectively inhibit HSP expression in advance, and then simultaneously enhanced the therapeutic efficacy of LTPTT. Further, both in vitro and in vivo experiments have demonstrated that the as-synthesized MAZG nanocomposite exhibited favorable biosafety and remarkable tumor growth inhibition.

Hepatocellular carcinoma is a common and highly malignant disease. As a currently designated systemic chemotherapeutic agent for advanced Hepatocellular carcinoma, sorafenib has been confronted with dilemma of drug-resistance caused by tumor hypoxia, which hinders the therapeutic efficacy of the drug. Based on this, a multifunctional mesoporous polydopamine nanoprobe 2Me-SPIO-CY5.5@AAZ-MPDA with a mesoporous frame loaded 2-Methoxyestradiol, Superparamagnetic Iron Oxide Nanoparticles and the near-infrared dye cyanine 5.5, conjugated with hypoxia Hepatocellular carcinoma-specific targeting molecule of sulfonamides acetazolamide, is fabricated for hypoxic region targeting, sorafenib resistance reversion and photothermal therapy of Hepatocellular carcinoma. In addition, the magnetic resonance imaging/fluorescence/photoacoustic tri-modal imaging ability enables the tracing of the nanoprobes and monitoring the treatment procedure in vivo, providing a new methods of imaging-guided Hepatocellular carcinoma synergic treatment which improves the long-term therapeutic effects of sorafenib.

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.

Photothermal therapy (PTT) is a promising method to kill pathogenic bacteria. However, using single-modal PTT, it is easy to cause tissue damage because of the overtemperature. Hence, it is necessary to combine PTT with other antibacterial strategies. In this study, we employed silver nanoparticles (Ag NPs) and mesoporous polydopamine (MPDA) nanoparticles to establish a multimodal antibacterial platform (MPDA@Ag). MPDA nanoparticles not only served as a photothermal transduction agent to convert light-energy to heat under the irradiation of near-infrared (NIR) light but also acted as a reducer to reduce Ag NPs in situ. Because Ag NPs can effectively kill bacteria, MPDA@Ag can overcome the drawbacks of the single-modal PTT antibacterial strategy, achieving a synergistic antibacterial effect. Moreover, as an antibiotic-free strategy, MPDA@Ag was less likely to induce drug resistance when killing bacteria. In summary, this platform offered a simple and practical means to achieve excellent antibacterial activity and supplied a good alternative to fight pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Theranostic nanodrugs combining magnetic resonance imaging (MRI) and cancer therapy have attracted extensive interest in cancer diagnosis and treatment. Herein, a manganese (Mn)-doped mesoporous polydopamine (Mn-MPDA) nanodrug incorporating the nitric oxide (NO) prodrug BNN6 and immune agonist R848 was developed. The nanodrug responded to the H+ and glutathione being enriched in tumor microenvironment to release R848 and Mn2+. The abundant Mn2+ produced through a Fenton-like reaction enabled a highly sensitive T1–T2 dual-mode MRI for monitoring the tumor accumulation process of the nanodrug, based on which an MRI-guided laser irradiation was achieved to trigger the NO gas therapy. Meanwhile, R848 induced the re-polarization of tumor-promoting M2-like macrophage to a tumoricidal M1 phenotype. Consequently, a potent synergistic antitumor effect was realized in mice bearing subcutaneous 4T1 breast cancer, which manifested the great promise of this multifunctional nanoplatform in cancer treatment. [ABSTRACT FROM AUTHOR]

Polydopamine (PDA) is a natural melanin derived from marine mussels that has good biocompatibility, biodegradability, and photothermal conversion ability. As a new coating material, it offers a novel way to modify the surface of various substances. The drug loading capacity and encapsulation efficiency of PDA are greatly improved via the use of mesoporous materials. The abundant pore canals on mesoporous polydopamine (MPDA) exhibit a uniquely large surface area, which provides a structural basis for drug delivery. In this review, we systematically summarized the characteristics and manufacturing process of MPDA, introduced its application in the diagnosis and treatment of cancer, and discussed the existing problems in its development and clinical application. This comprehensive review will facilitate further research on MPDA in the fields of medicine including cancer therapy, materials science, and biology. [ABSTRACT FROM AUTHOR]

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy, and it was very critical of constructing tumor microenvironment (TME)-responsive delivery nanocarriers, achieving the modulation release of drugs. Herein, using manganese dioxide (MnO2) as gatekeeper, an intelligent nanoplatform based on mesoporous polydopamine (MPDA) was developed to deliver doxorubicin (DOX), by which the DOX release was precisely controlled, and simultaneously the photothermal therapy (PTT) and chemodynamic therapy (CDT) were realized. In normal physiological environment, the stable MnO2 shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO2 shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn2+ further accelerated the cell death. Thus, the developed MPDA-DOX@MnO2 nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hypoxia and high accumulation of lactic acid in the tumor microenvironment provide fertile soil for tumor development, maintenance and metastasis. Herein, we developed a calcium peroxide (CaO2)-loaded nanostructure that can play a role of "one stone kill two birds", i.e., acidic and hypoxic tumor microenvironment can be simultaneously regulated by CaO2 loaded nanostructure. Specifically, CaO2-loaded mesoporous polydopamine nanoparticles modified with sodium hyaluronate (denoted as CaO2@mPDA-SH) can gradually accumulate in a tumor site. CaO2 exposed in acidic microenvironment can succeed in consuming the lactic acid with oxygen generation simultaneously, which could remodel the acid and hypoxia tumor microenvironment. More importantly, the relief of hypoxia could further reduce lactate production from the source by down-regulating the hypoxia inducible factor-1α (HIF-1α), which further down-regulated the glycolysis associated enzymes including glycolysis-related glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). As a result, CaO2@mPDA-SH alone without the employment of other therapeutics can dually regulate the tumor hypoxia and lactic acid metabolism, which efficiently represses tumor progression in promoting immune activation, antitumor metastasis, and anti-angiogenesis. [ABSTRACT FROM AUTHOR]

Chemotherapy is a common method for tumor treatment. However, the non-specific distribution of chemotherapeutic drugs causes the death of normal cells. Nanocarriers, particularly mesoporous carriers, can be modified to achieve targeted and controlled drug release. In this study, mesoporous polydopamine (MPDA) was used as a carrier for the antitumor drug doxorubicin (DOX). To enhance the release efficiency of DOX in the tumor microenvironment, which contains high concentrations of glutathione (GSH), we used N,N-bis(acryloyl)cysteamine as a cross-linking agent to encapsulate the surface of MPDA with fucoidan (FU), producing MPDA-DOX@FU-SS. MPDA-DOX@FU-SS was characterized via transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS), and its antitumor efficacy in vitro was investigated. The optimal conditions for the preparation of MPDA were identified as pH 12 and 20 °C, and the optimal MPDA-to-FU ratio was 2:1. The DOX release rate reached 47.77% in an in vitro solution containing 10 mM GSH at pH 5.2. When combined with photothermal therapy, MPDA-DOX@FU-SS significantly inhibited the growth of HCT-116 cells. In conclusion, MPDA-DOX@FU-SS may serve as a novel, highly effective tumor suppressor that can achieve targeted drug release in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

As a promising therapy, photothermal therapy (PTT) converts near-infrared (NIR) light into heat through efficient photothermal agents (PTAs), causing a rapid increase in local temperature. Considering the importance of PTAs in the clinical application of PTT, the safety of PTAs should be carefully evaluated before their widespread use. As a promising PTA, mesoporous polydopamine (MPDA) was studied for its clinical applications for tumor photothermal therapy and drug delivery. Given the important role that intestinal microflora plays in health, the impacts of MPDA on the intestine and on intestinal microflora were systematically evaluated in this study. Through biological and animal experiments, it was found that MPDA exhibited excellent biocompatibility, in vitro and in vivo. Moreover, 16S rRNA analysis demonstrated that there was no obvious difference in the composition and classification of intestinal microflora between different drug delivery groups and the control group. The results provided new evidence that MPDA was safe to use in large doses via different drug delivery means, and this lays the foundation for further clinical applications. [ABSTRACT FROM AUTHOR]

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 (ZrO 2 ) 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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract Background Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds. Methods In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice. Results Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis. Conclusions Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy. Graphic abstract

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. • A novel hypotensive nano-eyedrop was developed based on mesoporous polydopamine nanoparticles. • MPDA-PEG@Brim exhibited enhanced efficacy in reducing intraocular pressure. • MPDA-PEG exhibited remarkable efficacy in scavenging diverse free radicals. • MPDA-PEG could alleviate ocular surface oxidative stress induced by benzalkonium chloride. [ABSTRACT FROM AUTHOR]

Recently, fibroblast activation protein (FAP), an overexpressed transmembrane protein of activated fibroblast in pulmonary fibrosis, has been considered as the new target for diagnosing and treating pulmonary fibrosis. In this work, mesoporous polydopamine (MPDA), which is facile prepared and easily modified, is developed as a carrier to load antifibrosis drug pirfenidone (PFD) and linking FAP inhibitor (FAPI) to realize lesion-targeted drug delivery for pulmonary fibrosis therapy. We have found that PFD@MPDA-FAPI is well biocompatible and with good properties of antifibrosis, when ICG labels MPDA-FAPI, the accumulation of the nanodrug at the fibrosis lung in vivo can be observed by NIR imaging, and the antifibrosis properties of PFD@MPDA-FAPI in vivo were also better than those of pure PFD and PFD@MPDA; therefore, the easily produced and biocompatible nanodrug PFD@MPDA-FAPI developed in this study is promising for further clinical translations in pulmonary fibrosis antifibrosis therapy.

Hepatic cancer is a serious disease with high morbidity and mortality. Theranostic agents with effective diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer. Herein, we aimed to develop a novel mesoporous polydopamine (MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging (MRI)-guided cancer chemo-photothermal therapy. Superparamagnetic iron oxide (SPIO)-loaded MPDA NPs (MPDA@SPIO) was firstly prepared, followed by modifying with a targeted molecule of sialic acid (SA) and chelating with Fe3+ (SA-MPDA@SPIO/Fe3+ NPs). After that, doxorubicin (DOX)-loaded SA-MPDA@SPIO/Fe3+ NPs (SA-MPDA@SPIO/DOX/Fe3+) was prepared for tumor theranostics. The prepared SAPEG-MPDA@SPIO/Fe3+ NPs were water-dispersible and biocompatible as evidenced by MTT assay. In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability, with relaxivity of being r1 = 4.29 mM−1s−1 and r2 = 105.53 mM−1s−1, respectively. SAPEG-MPDA@SPIO/Fe3+ NPs could effectively encapsulate the DOX, showing dual pH- and thermal-triggered drug release behavior. In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe3+ NPs could effectively target to the hepatic tumor tissue, which was possibly due to the specific interaction between SA and the overexpressed E-selectin. This behavior also endowed SA-MPDA@SPIO/DOX/Fe3+ NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification. In addition, SAPEG-MPDA@SPIO/DOX/Fe3+ NPs displayed a superior therapeutic effect, which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy. These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe3+ NPs is an effective targeted nanoplatform for tumor theranostics, having potential value in the effective treatment of hepatic cancer.

Abstract Background Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O2 production, which in turn serves as a “radiosensitizer” to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. Results Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O2. ZHer2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of ZHer2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. Conclusions The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics. Graphic abstract

The design and preparation of multifunctional drug carriers for combined photothermal–chemotherapy of cancer have attracted extensive attention over the past few decades. However, the development of simple-structured stimuli-responsive theranostic agents as both photothermal agents and chemotherapeutic agents remains a big challenge. Herein, a novel double-shelled nanocarrier composed of hollow Ag2S (HAg2S) nanospheres and a mesoporous polydopamine (MPDA) exterior shell was fabricated through a facile process. Notably, HAg2S possesses both fluorescence and photothermal properties. MPDA acts as a drug carrier and photothermal agent. Meanwhile, the cavity structure between HAg2S and MPDA provides more space for drug loading. The nanocarrier presents a high drug loading rate of 23.4%. It exhibits an apparent pH-responsive DOX release property due to the acidic sensitivity of PDA. In addition, the release of DOX is promoted under NIR irradiation, which is attributed to the heating action generated by the photothermal effect of HAg2S and MPDA. The cytotoxicity test shows that the nanocarriers possess good biocompatibility. Compared with single photothermal therapy or chemotherapy, the combined treatment represents a synergistic effect with higher therapeutic efficacy. In addition, the nanocarriers exhibit excellent fluorescence imaging capability and can target HepG2 cells. These simple-structured smart nanocarriers have a great potential for fluorescence-mediated combination cancer therapy. [ABSTRACT FROM AUTHOR]

Traditional anticancer treatments fail to significantly improve prognoses, and exploration of novel promising therapeutic modalities is urgently needed. In this study, multifunctional mesoporous polydopamine nanoparticles (Pt@MPDA/GOx/Fe3+ NPs) loaded with glucose oxidase (GOx), Fe ions and ultrasmall Pt nanoparticles (NPs) were prepared for magnetic resonance imaging (MRI)-guided photothermal therapy (PTT)-enhanced chemodynamic therapy (CDT). The oxidation of intratumoral glucose to H2O2 and GOx induced an H2O2-rich microenvironment, and then elevated H2O2 was catalyzed into highly cytotoxic·OH by Fe3+ via a Fenton reaction for CDT to induce cancer cell death efficiently. Notably, the heat generated by MPDA NPs under laser irradiation offered a moderate PTT to cascade the CDT effect. Moreover, Pt NPs can oxidize H2O2 to yield O2, which in turn accelerates the catalytic process of GOx to increase the efficiency of CDT. Meanwhile, in the high oxidation environment of tumor cells, Pt NPs are oxidized into Pt2+ to achieve a tumor chemotherapy effect. In addition, chelated Fe3+ endows the system with an MRI-visible function to monitor the treatment efficacy. In conclusion, this study provides a novel MRI-guided PTT-enhanced CDT synergistic nanomedicine platform for cancer therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] Cancer phototherapy has attracted increasing attention for its effectiveness, relatively low side effect, and noninvasiveness. The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has been shown to exhibit promising prospects in cancer treatment. However, the tumor hypoxia, high level of intracellular glutathione (GSH), and insufficient photosensitizer uptake significantly limit the PDT efficacy. In this work, we combine oxygen supply, GSH depletion, and tumor targeting in one nanoplatform, folate-decorated mesoporous polydopamine nanoparticles (FA-MPPD) co-loaded with new indocyanine green (IR-820) and perfluorooctane (PFO) (IR-820/PFO@FA-MPPD), to overcome the PDT resistance for enhanced cancer PDT/PTT. IR-820/PFO@FA-MPPD exhibit efficient singlet oxygen generation and photothermal effect under 808 nm laser irradiation, GSH-promoted IR-820 release, and efficient cellular uptake, resulting in high intracellular reactive oxygen species (ROS) level under 808 nm laser irradiation and strong photocytotoxicity in vitro. Following intratumoral injection, IR-820/PFO@FA-MPPD can relieve tumor hypoxia sustainably by PFO-mediated oxygen transport and deplete intracellular GSH by the Michael addition reaction, which boost the PDT effect and lead to the most potent antitumor effect upon 808 nm laser irradiation. The multifunctional IR-820/PFO@FA-MPPD developed in this work offer a relatively simple and effective strategy to potentiate PDT for efficient cancer phototherapy. [ABSTRACT FROM AUTHOR]

A versatile theranostic agent that integrated with therapeutic and diagnostic functions is extremely essential for cancer theranostic. Herein, a multifunctional theranostic nanoplatform (PFP@MPDA-DOX) based on perfluoropentane (PFP) encapsulated mesoporous polydopamine (MPDA) is elaborately designed, followed by gating of drug doxorubicin (DOX) for preventing cargo leaking. The MPDA with pH-responsive biodegradation behavior was served as nanocarrier, which also endows the nanoplatform with a large cavity for PFP filling. The nanoparticles were then gated with DOX molecule by Michael addition and/or Schiff base reaction to shield the leaking of PFP during the blood circulation before the tumor tissue is reached. Also, such nanotheranostic exhibits high photothermal conversion efficiency of 45.6%, which can act as an intelligent nanosystem for photothermal therapy (PTT) and photoacoustic (PA) imaging. Moreover, the liquid-gas phase transition of PFP arising upon exposure to an 808 nm laser and thus produced the bubbles for ultrasound (US) imaging. The subsequent PFP@MPDA-DOX-mediated synergetic chemotherapy (contributed by the DOX gatekeeper) and PTT (contributed by the MPDA) shows excellent anticancer activity, which has been systematically evaluated both in vitro and in vivo. All these positive results certify that the facile incorporation of the antitumor drug gatekeeper and MPDA into one theranostic nanoplatform shows general potential for multimode PA/US imaging and combination chemotherapy/PTT of tumors.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024 Wiley‐VCH GmbH.)

Immunotherapy utilizing anti-PD-L1 blockade has achieved dramatic success in clinical breast cancer management but is often hampered by the limited immune response. Increasing evidence shows that immunogenic cell death (ICD) recently arises as a promising strategy for enlarging tumor immunogenicity and eliciting systemic anti-tumor immunity effectively. However, developing simple but versatile, highly efficient but low-toxic, biosafe, and clinically available transformed ICD inducers remains a huge demand and is highly desirable. Herein, a multifunctional ICD inducer is purposefully developed A6-MPDA@PAL by integrating photothermal therapy (PTT) nanoplatforms mesoporous polydopamine (MPDA), CDK4/6 inhibitor palbociclib (PAL), and CD44-specific targeting A6 peptide in a simple way for augmenting the immune antitumor efficacy of anti-PD-L1 therapy. Remarkably, the light-inducible nanoplatforms exhibit multiple favorable therapeutic features ensuring a superior and biosafe PTT/chemotherapy efficacy. Together with stronger accumulative ICD induction, single administration of A6-MPDA@PAL can trigger robust systemic antitumor immunity and abscopal effect with the assistance of anti-PD-L1 blockade by fascinating the intratumoral infiltration of T lymphocytes and reversing the immunosuppressive tumor microenvironment simultaneously, therapy achieving brilliant synergistic immunotherapy with effective tumor ablation. This study presents a simple and smart ICD inducer opening up attractive clinical possibilities for reinforcing the anti-PD-L1 therapy against breast cancer., (© 2024 Wiley‐VCH GmbH.)

Objectives: It is imperative to develop efficient strategies on the treatment of prostate cancer. Here, we constructed multifunctional nanoparticles, namely AS1411@MPDA‐DTX (AMD) for targeted and synergistic chemotherapy/photothermal therapy of prostate cancer. Materials and Methods: Mesoporous polydopamine (MPDA) nanoparticles were prepared by a one‐pot synthesis method, DTX was loaded through incubation, and AS1411 aptamer was modified onto MPDA by the covalent reaction. The prepared nanoparticles were characterized by ultra‐micro spectrophotometer, Fourier transform infrared spectra, transmission electron microscope, and so on. The targeting ability was detected by selective uptake and cell killing. The mechanism of AMD‐mediated synergistic therapy was detected by Western blot and immunofluorescence. Results: The prepared nanoparticles can be easily synthesized and possessed excellent water solubility, stability, and controlled drug release ability, preferentially in acidic context. Based on in vitro and in vivo results, the nanoparticles can efficiently target prostate cancer cells, promote DTX internalization, and enhance the antitumor effects of chemo‐photothermal therapy strategies under the NIR laser irradiation. Conclusions: As a multifunctional nanoplatform, AS1411@MPDA‐DTX could efficiently target prostate cancer cells, promote DTX internalization, and synergistically enhance the antiprostate cancer efficiency by combining with NIR irradiation. [ABSTRACT FROM AUTHOR]

Background: Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds. Methods: In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice. Results: Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis. Conclusions: Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy. [ABSTRACT FROM AUTHOR]

Polydopamine (PDA) is a natural melanin derived from marine mussels that has good biocompatibility, biodegradability, and photothermal conversion ability. As a new coating material, it offers a novel way to modify the surface of various substances. The drug loading capacity and encapsulation efficiency of PDA are greatly improved via the use of mesoporous materials. The abundant pore canals on mesoporous polydopamine (MPDA) exhibit a uniquely large surface area, which provides a structural basis for drug delivery. In this review, we systematically summarized the characteristics and manufacturing process of MPDA, introduced its application in the diagnosis and treatment of cancer, and discussed the existing problems in its development and clinical application. This comprehensive review will facilitate further research on MPDA in the fields of medicine including cancer therapy, materials science, and biology.

Chemotherapy is a common method for tumor treatment. However, the non-specific distribution of chemotherapeutic drugs causes the death of normal cells. Nanocarriers, particularly mesoporous carriers, can be modified to achieve targeted and controlled drug release. In this study, mesoporous polydopamine (MPDA) was used as a carrier for the antitumor drug doxorubicin (DOX). To enhance the release efficiency of DOX in the tumor microenvironment, which contains high concentrations of glutathione (GSH), we used N,N-bis(acryloyl)cysteamine as a cross-linking agent to encapsulate the surface of MPDA with fucoidan (FU), producing MPDA-DOX@FU-SS. MPDA-DOX@FU-SS was characterized via transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS), and its antitumor efficacy in vitro was investigated. The optimal conditions for the preparation of MPDA were identified as pH 12 and 20 °C, and the optimal MPDA-to-FU ratio was 2:1. The DOX release rate reached 47.77% in an in vitro solution containing 10 mM GSH at pH 5.2. When combined with photothermal therapy, MPDA-DOX@FU-SS significantly inhibited the growth of HCT-116 cells. In conclusion, MPDA-DOX@FU-SS may serve as a novel, highly effective tumor suppressor that can achieve targeted drug release in the tumor microenvironment.

[Display omitted] 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 MnO 2 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/MnO 2 NPs were found to have a particle size of approximately 198 nm. MnO 2 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 H 2 O 2 in cells. Mn2+ can catalyze the conversion of H 2 O 2 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/MnO 2 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. [ABSTRACT FROM AUTHOR]

This study reports a smart theranostic probe, designated as DMCR, designed for simultaneous CT/MR/FL imaging and chemo/photothermal synergistic therapy. Gd/I-doped carbon nanodots (designed as Gd/I-CDs) are synthesized for the first time using a straightforward one-step solvent thermal approach, serving as the efficient FL/MR/CT trimodal imaging component of DMCR. Subsequently, chemical drug doxorubicin (DOX), diagnostic moiety Gd/I-CDs and tumor-targeting peptide CRGD are successively conjugated onto mesoporous polydopamine (MPDA) to prepare DMCR. Besides its role as versatile scaffold for loading various functional moieties, MPDA serves two additional functions: as an efficient fluorescence quencher for Gd/I-CDs, and an effective photo-sensitizer for photothermal therapy. Therefore, loading DOX into MPDA facilitates the resulting DMCR for chemo/photothermal synergistic tumor therapy. DMCR exhibits excellent water-solubility, biocompatibility, and strong tumor-targeting capability. The decomposition of MPDA by over-expressed glutathione (GSH) and H+ in the tumor microenvironment leads to the GSH/H+-responsive release of diagnostic moieties Gd/I-CDs and therapeutic moieties DOX, triggering the fluorescence turn-on of Gd/I-CDs. In addition, DMCR exhibits a high r 1 relaxation rate (38.3 mM−1s−1) and X-ray absorption capability (153.8 Hu mM−1). Both in vitro and in vivo experiments confirm DMCR's high effectiveness in FL/MR/CT triple-modal imaging of tumors and synergistically inhibiting tumor growth with improved efficacy. [Display omitted] [ABSTRACT FROM AUTHOR]