Effect of biophysical properties of tumor extracellular matrix on intratumoral fate of nanoparticles: Implications on the design of nanomedicine.

Nanomedicine has a profound impact on various research domains including drug delivery, diagnostics, theranostics, and regenerative medicine. Nevertheless, the clinical translation of nanomedicines for solid cancer remains limited due to the abundant physiological and pathological barriers in tumor that hinder the intratumoral penetration and distribution of these nanomedicines. In this article, we review the dynamic remodeling of tumor extracellular matrix during the tumor progression, discuss the impact of biophysical obstacles within tumors on the penetration and distribution of nanomedicines within the solid tumor and collect innovative approaches to surmount these obstacles for improving the penetration and accumulation of nanomedicines in tumor. Furthermore, we dissect the challenges and opportunities of the respective approaches, and propose potential avenues for future investigations. The purpose of this review is to provide a perspective guideline on how to effectively enhance the penetration of nanomedicines within tumors using promising methods.

An Overview of Polymeric Nanoplatforms to Deliver Veterinary Antimicrobials.

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.

A multifunctional switching bidirectional optical absorber based on a titanium nitride metamaterial.

In this paper, a novel type of tunable ultra-wide band and double-narrow band artificial electromagnetic absorption device is studied. This work uses a titanium nitride-titanium-tungsten (TiN-Ti-W) composite ring array, a TiN reflector layer, and a silver-titanium dioxide-silver (Ag-TiO2-Ag) three layer composite structure to prepare the absorption layer. The simulation results illustrate that the absorption rate can reach 96.6% when the absorption wavelength is 300-2800 nm. When the light source is backward incidence, ultra-narrow band absorption can occur at specific wavelengths of 465 nm and 932 nm. This proves that the absorber is in good agreement with the impedance matching theory. The research results of this work will provide a theoretical basis for the design and application of solar thermal energy conversion.

Ultrasound-guided microwave ablation for tertiary hyperparathyroidism in patients with renal transplantation.

OBJECTIVE: To explore the safety and efficacy of ultrasound-guided microwave ablation (MWA) for tertiary hyperparathyroidism (THPT) in patients with renal transplantation (RT). METHODS: In total, fifteen patients with THPT after renal transplantation who underwent MWA were enrolled in the study. The pre- and post-MWA intact parathyroid hormone (iPTH), serum calcium, phosphorus, creatinine, urea nitrogen and estimated glomerular filtration rate (eGFR) values were compared. RESULTS: A total of 38 parathyroid hyperplastic nodules in 15 RT patients were treated with ultrasound-guided MWA. The mean (median, range) size of the hyperplastic parathyroid nodules was 11.5 mm (11 mm, 5-25 mm), and the average (median, range) ablation time was 163.5s (121 s, 44-406 s). The average levels of serum iPTH and calcium at 1 d, 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly lower than those pre-MWA (all p < 0.05). Compared with the pre-MWA value (0.76 mmol/L), the serum phosphorus levels at 1 d post-MWA (0.63 mmol/L) were significantly decreased, and those at 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly increased, but all were within the normal range. There was no significant difference in serum creatinine and eGFR pre-MWA and post-MWA. No major MWA-related complications occurred. CONCLUSION: Ultrasound-guided MWA shows potential as a viable treatment for THPT in RT patients. However, further studies are required to confirm its safety and effectiveness in larger cohorts of longer duration.

Metamaterial ultra-wideband solar absorbers based on a multi-layer structure with cross etching.

In this paper, we design a solar absorber based on the Si3N4-W-Ti-SiO2 insulator-metal-insulator structure and demonstrate it using the finite difference time domain (FDTD) method. The absorption rate of the absorber consisting of a multi-layer structure with cross etching is over 90% in the bandwidth of 500 nm to 2995 nm with an average absorption rate of 98.3%. There are three peaks at 620 nm, 1002 nm and 1761 nm with peak heights of 99.8%, 99.8% and 99.0%, respectively. By analyzing the distribution of electric and magnetic fields in different sections of the absorber, it is found that the physical mechanism of the structure with high absorptivity is due to the interaction of propagating surface plasmon resonance and local surface plasma resonance. The effects of different structural parameters and the angle of incidence of a light source on the absorber absorption are discussed. The absorber can be used in solar thermal systems, thermal photovoltaics and thermoelectronic devices.

Case report: Thoughts on two cases of total anomalous pulmonary venous connection complicated with pulmonary artery hypertension.

The two primary pathological alterations of total anomalous pulmonary venous connection (TAPVC), a rare cyanotic congenital heart disease (CHD), are right heart failure and pulmonary artery hypertension (PAH). The timing and prognosis of surgery depend on the level of pulmonary hypertension. Surgery will not be an option after Eisenmenger syndrome appears. In light of this, it is crucial to assess patients' PAH. In order to aid in the following treatment of related types of diseases, this article studied and compared the echocardiographic features and disease development of one adult and one child TAPVC patients complicated with PAH.

Alterations of CD8+ T cells in the blood and salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVE: To identify the alterations of CD8+ T cells in blood and labial salivary glands (LSGs) of patients with Primary Sjögren's syndrome (pSS). METHODS: Blood samples from 24 pSS patients were assayed for CD38+ HLA-DR+ CD8+ (activated CD8+, aCD8+) T cells and serum IFN-γ and TNF-α, using flow cytometry and ELISA respectively, and compared with samples from 27 healthy controls. Immunohistochemistry was used to count CD8+ T cells in LSG tissues of 24 pSS patients and of 6 control patients with normal pathology. RESULTS: pSS patients had more aCD8+ T cells than aCD4+ T cells (medians 33.13% vs. 9.43%, p < 0.0001), and had an increased level of aCD8+ T cells (medians 33.13% vs. 16.48%, p < 0.0001) and serum IFN-γ (medians 1026 pg/mL vs. 0.00 pg/mL, p < 0.0001) compared to the healthy controls. The levels of aCD8+ T cells and IFN-γ were both significant positively correlated with European League Against Rheumatism Sjögren's Syndrome Disease Activity Index, IgG, anti-nuclear antibodies, rheumatoid factor. The LSGs focus score (FS) ≥1 group had more CD8+ T cell counts than 0≤ FS <1 group and control group (medians 256/mm2 vs. 126/mm2 and 256/mm2 vs. 64/mm2 respectively, both p < 0.05). CONCLUSION: The aCD8+ T cells and IFN-γ are positively correlated with each other, and predominantly elevated in the blood of pSS patients. In the LSG tissues of pSS, CD8+ T cell counts increase with severity of the lesions. CD8+ T cells may play crucial role in the pathogenesis of pSS. Key Points • Primary Sjögren's syndrome (pSS) is a chronic and systemic autoimmune disease. pSS patients had elevated blood levels of CD38 + HLA-DR+ CD8+ T cells and IFN-γ. • The CD38 + HLA-DR+ CD8+ T cells positively correlated with disease parameters and serum IFN-γ. • The salivary glands of pSS patients had appreciable CD8 + lymphocyte infiltration. CD8+ T cells may play crucial role in the pathogenesis of pSS.

The Yin and Yang of the protein corona on the delivery journey of nanoparticles.

Nanoparticles-based drug delivery systems have attracted significant attention in biomedical fields because they can deliver loaded cargoes to the target site in a controlled manner. However, tremendous challenges must still be overcome to reach the expected targeting and therapeutic efficacy in vivo. These challenges mainly arise because the interaction between nanoparticles and biological systems is complex and dynamic and is influenced by the physicochemical properties of the nanoparticles and the heterogeneity of biological systems. Importantly, once the nanoparticles are injected into the blood, a protein corona will inevitably form on the surface. The protein corona creates a new biological identity which plays a vital role in mediating the bio-nano interaction and determining the ultimate results. Thus, it is essential to understand how the protein corona affects the delivery journey of nanoparticles in vivo and what we can do to exploit the protein corona for better delivery efficiency. In this review, we first summarize the fundamental impact of the protein corona on the delivery journey of nanoparticles. Next, we emphasize the strategies that have been developed for tailoring and exploiting the protein corona to improve the transportation behavior of nanoparticles in vivo. Finally, we highlight what we need to do as a next step towards better understanding and exploitation of the protein corona. We hope these insights into the "Yin and Yang" effect of the protein corona will have profound implications for understanding the role of the protein corona in a wide range of nanoparticles.

Characteristics of Patients with Primary Sjögren's Syndrome and Non-specific Chronic Sialadenitis: A Subtype in Elderly Patients.

INTRODUCTION: Non-specific chronic sialadenitis (NSCS) is a common pathology of labial salivary glands (LSGs), and NSCS with positive anti-SSA/SSB antibodies is common in clinical practice. Previous studies have evaluated the associations of high focus score (FS) with clinical manifestations in primary Sjögren's syndrome (pSS) patients extensively, but the characteristics of pSS with NSCS have seldom been investigated. We here analyzed the characteristics of pSS patients with NSCS. METHODS: Among 425 patients who underwent LSG biopsies, 217 had pSS and 37 non-SS sicca patients had NSCS without other diseases (i.e., sicca controls). We categorized these 217 pSS patients into three groups based on the pathology of LSGs: FS ≥ 1 (n = 104), 0 ≤ FS < 1 (n = 76), and NSCS (n = 37). We then compared the three groups while focusing on the NSCS group. Multivariate logistic regression analysis was performed to identify variables that influenced NSCS. RESULTS: The mean age of pSS patients with NSCS (58.3 ± 11.0 years) was significantly higher than those with FS ≥ 1 (48.5 ± 14.9 years) and 0 ≤ FS < 1 (45.3 ± 13.7 years), but other clinical characteristics were similar. NSCS had a significant positive correlation with age (OR = 7.282, 95% CI 2.085-25.44 and OR = 13.130, 95% CI 3.368-51.189 for patients aged 45-64 years and > 65 years, respectively). Significantly higher levels of lymphocytic infiltration were found in the pSS NSCS group than in the sicca NSCS controls (48.6 vs. 10.8%, respectively). CONCLUSIONS: The pSS patients with NSCS were older than corresponding non-NSCS pSS individuals, but they had similar clinical features. NSCS is associated with age and seldom occurred below the age of 45 years, regardless of the presence or absence of pSS. NSCS may be a subtype of pSS in elderly patients.

Calcium alginate/PNIPAAm hydrogel with body temperature response and great biocompatibility: Application as burn wound dressing.

Deep burns often do not heal easily, because the dermis of the skin is severely damaged, leading to severe inflammation and bacterial infection. Therefore, it is of great clinical significance to develop a dressing that promotes the healing process of deep burn wound. In this study, we used N-isopropyl acrylamide, sodium alginate and calcium chloride as the main materials, a series of calcium alginate/ poly (N-isopropyl acrylamide)(NIPAAm) hydrogel (CAPH) with different component ratios were synthesized. Its swelling properties, temperature response properties, rheological properties, biocompatibility properties, and in vitro drug release properties were investigated. Based on the above conditions, the CAPH(sodium alginate:NIPAAm = 2:15) with the best comprehensive performance was selected, which has a good biocompatibility. In addition, 0.02 % (w/v) mupirocin was loaded in CAPH. The temperature-responsive property of PNIPAAm in CAPH at 34 °C not only allowed the CAPH to rapidly release the drug under to prevent infection, but also to assist in wound contraction. Application of CAPH to localized wounds of deep second-degree burns in mice showed a faster healing rate and tissue regeneration. At the same time, collagen recovery was enhanced, collagen bundles were arranged in an orderly manner, and the scarring was not obvious after 16 days. Therefore, this research prepared a new safe and effective biomaterial.

A WeChat-Based Rehabilitation Platform for Children and Adolescents with Congenital Heart Disease to Promote Cardiac FITness (HeartFIT): Protocol for a Mixed-Methods Strategy from Evidence-Based Design to Pilot Study.

Progress in medical and surgical care has tremendously improved the survival rates of children with congenital heart disease (CHD). However, reduced aerobic capacity and health-related issues remain a threaten to quality survival and prevention of related complications among children and adolescents with CHD. This research program aims to develop and evaluate a WeChat-based health platform (HeartFIT) to facilitate cardiac rehabilitation and promote physical fitness for this rapidly expanding young population. The study protocol describes the use of an iterative process of using a mixed-methods strategy to develop, refine, and pilot test the proposed HeartFIT platform. A sequential problem-solving process comprising four iterative phases with ongoing end-user input will be implemented. In phase 1, relevant literature was systematically reviewed (completed) and then child-parent dyads will be interviewed to understand the broad context and the requirements and considerations of the target population toward the WeChat-based rehabilitation platform. In phase 2, key features and priority functionalities for the platform will be ideated and refined, and a digital interactive prototype will be created. In phase 3, heuristic evaluation and three rounds of end-user testing will be conducted to ensure further refinement and usability of the prototype. In phase 4, a prospective pilot study will be performed to investigate the feasibility, acceptability, and preliminary efficacy of the developed platform over a 12-week intervention period. If HeartFIT intervention is feasible, acceptable, and demonstrates promising efficacy, an adequately powered randomized controlled trial (future work) will be deployed to test the real-world effectiveness of the intervention.

A hydrogel based on nanocellulose/polydopamine/gelatin used for the treatment of MRSA infected wounds with broad-spectrum antibacterial and antioxidant properties and tissue suitability.

Most wound dressings encounter a series of problems when dealing with the bacterial infection of wounds, for example, the antibacterial and antioxidant capacities, comfort, and mechanical properties are not suitable to meet clinical requirements. Here, we synthesized ε-polylysine-grafted nanocellulose (NCF-EPL) and polydopamine (PDA) nanoparticles and embedded them in genipin-cross-linked gelatin to prepare a hydrogel (NCF-EPL/GTP/PDA). In this system, the embedded NCF-EPL and PDA interact with the gelatin matrix to form a hydrogel with excellent physical properties. The hydrogel has broad-spectrum antibacterial abilities and good antioxidant performance, and it can effectively promote cell proliferation. Full-thickness MRSA-infected skin wound healing experiments clearly show that the NCF-EPL/GTP/PDA hydrogel can significantly accelerate the healing of infected wounds via killing bacteria and reducing inflammation, and secondary damage caused by adhesion during dressing use is effectively avoided. In short, the hydrogel provides a new method for overcoming the shortcomings of traditional dressings, and this approach provides further solutions for the selection of clinical dressings for healing wounds.

A Redox-Activatable and Targeted Photosensitizing Agent to Deliver Doxorubicin for Combining Chemotherapy and Photodynamic Therapy.

Currently, tumors have become a serious disease threatening human health and life in modern society. Photo-chemo combination therapy is considered to be an important method to improving the efficiency of tumor treatment, especially in the treatment of multi-drug-resistant tumors. However, the application of photo-chemo combination therapy has been limited by the poor water solubility of photosensitizers, low tumor targeting, and high side effects of chemotherapy drugs. In order to solve these problems, a smart nano drug delivery platform FA-PEG-ss-PLL(-g-Ce6) designed and synthesized by us. The smart nano drug carrier uses folic acid (FA) as the targeting group, polyethylene glycol (PEG) as the hydrophilic end, Ce6-grafted polylysine (PLL(-g-Ce6)) as the hydrophobic end, and Chlorin e6 (Ce6) as the photosensitizer of photodynamic therapy, and it connects PEG to PLL by a redox-responsive cleavable disulfide linker (-ss-). Finally, the combination of tumor chemotherapy and photodynamic therapy (PDT) is realized by loading with anticancer drug doxorubicin (DOX) to the intelligent carrier. In vitro experiments showed that the drug loading content (DLC%) of DOX@FA-PEG-ss-PLL(-g-Ce6) nanoparticles (DOX@FPLC NPs) was as high as 14.83%, and the nanoparticles had good serum stability, reduction sensitivity and hemocompatibility. From the cytotoxicity assays in vitro, we found that under 664 nm laser irradiation DOX@FPLC NPs showed stronger toxicity to MCF-7 cells than did DOX, Ce6 + laser, and DOX + Ce6 + laser. Moreover, the antitumor efficiency in vivo and histopathological analysis showed that DOX@FPLC NPs under 664 nm laser irradiation exhibited higher antitumor activity and lower systemic toxicity than single chemotherapy. These results suggested that the FA-PEG-ss-PLL(-g-Ce6) nano drug delivery platform has considerable potential for the combination of chemotherapy and PDT.

Self-Assembly of Podophyllotoxin-Loaded Lipid Bilayer Nanoparticles for Highly Effective Chemotherapy and Immunotherapy via Downregulation of Programmed Cell Death Ligand 1 Production.

Low drug delivery efficiency elevates the cost of medication, lowers the therapeutic efficacy, and appears as a leading reason for unmet needs in anticancer therapies. Herein, we report the development of self-assembled podophyllotoxin-loaded lipid bilayer nanoparticles that inhibit the production of programmed cell death ligand 1 in lung cancer cells and promote tumor-specific immune responses, thus offering a strategy for regulating the immunosuppressive microenvironment of tumors. In addition, encapsulation of podophyllotoxin in the nanoparticles reduced its systemic toxicity, enhanced its penetration into tumors, and increased its antitumor efficacy. Systemic injection of the nanoparticles into tumor-bearing mice not only prevented tumor immune escape but also significantly inhibited tumor growth and extended survival. In general, the podophyllotoxin-loaded nanoparticles exhibited both immunological effects and antitumor effects in addition to having better targeting activity and fewer side effects than free podophyllotoxin. We expect our findings to facilitate the development of therapies for lung cancer.

Leonurine hydrochloride-a new drug for the treatment of menopausal syndrome: Synthesis, estrogen-like effects and pharmacokinetics.

This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through 1H NMR and mass spectrometry (MS). Then the estrogenic activity of Leo in vitro and in vivo was studied. The proliferation and proliferation inhibitory effects of Leo on MCF-7 cells and MDA-MB-231 cells indicate that Leo exerts estrogen-like effects through estrogen receptor α (ERα) and estrogen receptor ß((ERß) in vitro. Uterotrophic assay in juvenile mice showed that Leo has an estrogen-like effect in vivo, as it can promote the development of the uterus of juvenile mice, increase its uterine coefficient and the size of the uterine cavity, as well as the increased number of uterine glands and the thickened uterine wall. For further research, cyclophosphamide (CTX) was used to establish a mouse model of ovarian function decline. Through this model, we found that Leo can restore the estrous cycle of mice, increase the number of primordial and primary follicles in the ovaries of mice, and regulate the disordered hypothalamic-pituitary-ovarian (HPOA) axis of mice. Finally, the pharmacokinetics of Leo was studied and oral bioavailability of Leo was calculated to be 2.21%. Leo was synthesized and the estrogen-like effect in vitro and in vivo was confirmed as well as its pharmacokinetics.

A heme-regulatable chemodynamic nanodrug harnessing transcription factor Bach1 against lung cancer metastasis.

Non-small cell lung cancer (NSCLC) is a type of cancer dominated by metastasis-induced death. The transcription factor BTB and CNC homology 1 (Bach1) regulates almost all metastasis steps by activating the transcription of critical metastatic genes. It is urgent to engineer a nanodrug enabling regulation of Bach1 against tumor metastasis. Herein, a minimalist nanodrug integrating chemodynamic therapy (CDT) and Bach1 degradation was reported to prevent metastasis of NSCLC. The nanodrug was achieved by self-assembly of ferrocene (Fc) and Tin protoporphyrin IX (TinPPIX). In our nanodrug, Fc not only triggers the production of highly cytotoxic ∙OH for tumor ablation via Fenton reaction, but also induces heme release from heme-containing proteins to stimulate Bach 1 degradation. Moreover, TinPPIX further augments the free heme level along with amplifies the CDT efficacy by disabling heme oxygenase-1 (HO-1)-mediated heme conversion into antioxidative bilirubin. The results showed that, compared with control group, TinPPIX/Fc nanodrug caused a four-fold increase in heme level, which triggered remarkable Bach1 degradation in Fbxo22-mediated manner and successfully inhibited Bach1-dominated metastasis. Therefore, this nanodrug could powerfully impeded NSCLC progression and metastasis, offering an innovative heme-regulatable chemodynamic therapeutic approach for lung cancer with strong metastasis capability.

Platelet-armored nanoplatform to harmonize janus-faced IFN-γ against tumor recurrence and metastasis.

Interferon-γ (IFN-γ) plays contradictory roles in tumor immunology: (I) to activate positive host's immunity for eliminating tumor; (II) to induce negative adaptive immune resistance via up-regulating programmed death ligand-1 (PD-L1) expression for tumors to evade immune surveillance. The negative feedback loop between the IFN-γ recovery and the IFN-γ-induced PD-L1 up-regulation puts postoperative adjuvant chemotherapy into a dilemma. It is of great significance but challenging to manipulate the double-edge effects of IFN-γ against postoperative tumor progression. Herein, a platelet-engineered nanoplatform (PMF@DR NPs) capable of harmonizing janus-faced nature of IFN-γ was designed via uniquely co-assembling doxorubicin (Dox) and cyclin-dependent kinase 5 inhibitor roscovitine (Rosco) with platelet membrane fragment (PMF) as the particulate stabilizer. With PMF@DR NPs navigated by PMF to residual tumor, the Dox-activated immune response recovered IFN-γ secretion for positive host's immunity, while the IFN-γ-induced negative adaptive immune resistance was potently overcome by Rosco via disabling PD-L1 expression without dependence of IFN-γ stimulation. The negative feedback loop between IFN-γ recovery and PD-L1 up-regulation was thus potently disrupted in postoperative adjuvant chemotherapy. Our PMF@DR NPs not only harmonized janus-faced nature of IFN-γ to effectively regulate postoperative tumor progression, but also illustrated an innovative strategy for high-drug-loading biomimic nanoplatform.

[Advances in autoantibodies and primary Sjogren's syndrome: An update].

One of the hallmarks of primary Sjogren's syndrome (pSS) is the presence of various autoantibodies in patients' serum, including traditional autoantibodies for disease diagnosis and classification, autoantibodies associated with other autoimmune diseases, and the novel autoantibodies identified from mouse models. The autoantibodies are closely related to the diagnosis, prognosis, and clinical manifestations of pSS. There are significant differences in the prevalence and clinical correlations between anti-Ro60 antibody and anti-Ro52 antibody. Also, the novel autoantibodies play an important role in the diagnosis and classification of pSS. These advances further improve the accuracy of pSS diagnosis and provide references for basic and clinical research.

Physical Exercise in Managing Takayasu Arteritis Patients Complicated With Cardiovascular Diseases.

Takayasu arteritis (TA) is a kind of large-vessel vasculitis that mainly affects the aorta and its branches, and the patients are usually women at a relatively young age. The chronic inflammation of arteries in TA patients leads to stenosis, occlusion, dilatation, or aneurysm formation. Patients with TA thereby have a high risk of cardiovascular disease (CVD) complications, which are the most common cause of mortality. This review summarizes the main cardiovascular complications and the risk factors of cardiovascular complications in patients with TA. Here, we discuss the benefits and potential risks of physical exercise in patients with TA and give recommendations about exercise prescription for TA patients to decrease the risks of CVD and facilitate rehabilitation of cardiovascular complications, which might maximally improve the outcomes.

A two-pronged photodynamic nanodrug to prevent metastasis of basal-like breast cancer.

A two-pronged concept combining photodynamic therapy (PDT) and epithelial-mesenchymal transition (EMT) blockade in a minimalist nanoplatform was proposed to combat basal-like breast cancer (BLBC) metastasis. Based on PDT-mediated tumor killing and epalrestat (Epa)-mediated EMT blockade, as-prepared Ce6/Epa nanoparticles prevented BLBC metastasis effectively in vivo, providing a very promising two-pronged strategy against BLBC metastasis.