Pectolinarigenin ameliorates osteoporosis via enhancing Wnt signaling cascade in PPARß-dependent manner.

BACKGROUND: Osteoporosis is a prevalent metabolic bone disease in older adults. Peroxisome proliferator-activated receptor ß (PPARß), the most abundant PPAR isotype expressed in bone tissues, plays a critical role in regulating the energy metabolism of osteoblasts. However, the botanical compounds targeting PPARß for the treatment of osteoporosis remain largely unexplored. PURPOSE: To discover a potent PPARß agonist from botanical compounds, as well as to investigate the anti-osteoporosis effects and to elucidate the underlying mechanisms of the newly identified PPARß agonist. METHODS: The PPARß agonist effects of botanical compounds were screened by an in vitro luciferase reporter gene assay. The PPARß agonist effects of pectolinarigenin (PEC) in bone marrow mesenchymal stromal cells (BMSCs) were validated by Western blotting. RNA-seq transcriptome analyses were conducted to reveal the underlying osteoporosis mechanisms of PEC in BMSCs. The PPARß antagonist (GSK0660) and Wnt signaling inhibitor (XAV969) were used to explore the role of the PPARß and Wnt signaling cascade in the anti-osteoporosis effects of PEC. PEC or the PEG-PLGA nanoparticles of PEC (PEC-NP) were intraperitoneally administrated in both wild-type mice and ovariectomy-induced osteoporosis mice to examine its anti-osteoporotic effects in vivo. RESULTS: PEC, a newly identified naturally occurring PPARß agonist, significantly promotes osteogenic differentiation and up-regulates the osteogenic differentiation-related genes (Runx2, Osterix, and Bmp2) in BMSCs. RNA sequencing and functional gene enrichment analysis suggested that PEC could activate osteogenic-related signaling pathways, including Wnt and PPAR signaling pathways. Further investigations suggested that PEC could enhance Wnt/ß-catenin signaling in a PPARß-dependent manner in BMSCs. Animal tests showed that PEC-NP promoted bone mass and density, increased the bone cell matrix protein, and accelerated bone formation in wild-type mice, while PEC-NP also played a preventive role in ovariectomy-induced osteoporosis mice via maintaining the expression level of bone cell matrix protein, balancing the rate of bone formation, and slowing down bone loss. Additionally, PEC-NP did not cause any organ injury and body weight loss after long-term use (11 weeks). CONCLUSION: PEC significantly promotes bone formation and reduces bone loss in both BMSCs and ovariectomy-induced osteoporosis mice via enhancing the Wnt signaling cascade in a PPARß-dependent manner, providing a new alternative therapy for preventing estrogen deficiency-induced osteoporotic diseases.

Nanomedicines for reversing immunosuppressive microenvironment of hepatocellular carcinoma.

Although immunotherapeutic strategies such as immune checkpoint inhibitors (ICIs) have gained promising advances, their limited efficacy and significant toxicity remain great challenges for hepatocellular carcinoma (HCC) immunotherapy. The tumor immunosuppressive microenvironment (TIME) with insufficient T-cell infiltration and low immunogenicity accounts for most HCC patients' poor response to ICIs. Worse still, the current immunotherapeutics without precise delivery may elicit enormous autoimmune side effects and systemic toxicity in the clinic. With a better understanding of the TIME in HCC, nanomedicines have emerged as an efficient strategy to achieve remodeling of the TIME and superadditive antitumor effects via targeted delivery of immunotherapeutics or multimodal synergistic therapy. Based on the typical characteristics of the TIME in HCC, this review summarizes the recent advancements in nanomedicine-based strategies for TIME-reversing HCC treatment. Additionally, perspectives on the awaiting challenges and opportunities of nanomedicines in modulating the TIME of HCC are presented. Acquisition of knowledge of nanomedicine-mediated TIME reversal will provide researchers with a better opportunity for clinical translation of HCC immunotherapy.

Effect of dietary and physical activity behavioral interventions on reducing postpartum weight retention among women with recent gestational diabetes: A systematic review and meta-analysis of randomized controlled trials.

Postpartum weight retention (PPWR) increases the risk of long-term obesity and metabolic disease in women with recent gestational diabetes mellitus (GDM). This systematic review aimed to assess the effectiveness of dietary and physical activity behavior interventions in reducing PPWR. We systematically searched 13 electronic databases to retrieve articles published in English or Chinese before October 22, 2022. Randomized controlled trials (RCTs) that assessed dietary and/or physical activity behaviors interventions on the outcomes of PPWR among women with recent GDM were included. Twelve studies researched a total of 5672 participants. The meta-analysis indicated that dietary and physical activity behaviors interventions showed significant effects on the pooled effect size of body weight changes (WMD = -2.19, 95% CIs: -3.39, -0.98 kg), body mass index (WMD = -0.98, 95% CIs: -1.56, -0.39 kg/m2 ), and waist circumference (WMD = -1.20, 95% CIs: -2.49, 0.08 cm). Furthermore, the intervention group was more likely to achieve weight reduction (OR = 0.76, 95% CIs: 0.67, 0.87) than the control group. Postpartum dietary and physical activity behavior interventions for women with a recent GDM can reduce PPWR, and 1 year postpartum may be a window of opportunity.

Body Weight Correlates with Molecular Variances in Patients with Cancer.

Overweight and obesity are identified by a high body mass index (BMI) and carry significant health risks due to associated comorbidities. Although epidemiologic data connect overweight/obesity with 13 cancer types, a better understanding of the molecular mechanisms underlying this correlation is needed to improve prevention and treatment strategies. In this study, we conducted a comprehensive analysis of molecular differences between overweight or obese patients and normal weight patients across 14 different cancer types from The Cancer Genome Atlas. Using the propensity score weighting algorithm to control for confounding factors, obesity-specific mutational features were identified, such as higher mutation burden in rectal cancer and biased mutational signatures in other cancers. Differentially expressed genes (DEG) in tumors from patients with overweight/obesity were predominantly upregulated and enriched in inflammatory and hormone-related pathways. These DEGs were significantly associated with survival rates in various cancer types, highlighting the impact of elevated body fat on gene expression profiles and clinical outcomes in patients with cancer. Interestingly, while high BMI seemed to have a negative impact on most cancer types, the normal weight-biased mutational and gene expression patterns indicated overweight/obesity may be beneficial in endometrial cancer, suggesting the presence of an "obesity paradox" in this context. Body fat also significantly impacted the tumor microenvironment by modulating immune cell infiltration, underscoring the importance of understanding the interplay between weight and immune response in cancer progression. Together, this study systematically elucidates the molecular differences corresponding to body weight in multiple cancer types, offering potentially critical insights for developing precision therapy for patients with cancer. SIGNIFICANCE: Elucidation of the complex interplay between body weight and the molecular landscape of cancer could potentially guide tailored therapies and improve patient management amid the global obesity crisis.

Effects of women with gestational diabetes mellitus related weight gain on pregnancy outcomes and its experiences in weight management programs: a mixed-methods systematic review.

Introduction: Proper controlling gestational diabetes mellitus (GDM)-related gestational weight gain (GWG) during pregnancy can optimize pregnancy outcomes and improve postpartum glucose homeostasis. This study aimed to explore the existing intervention programs, the effects on pregnancy outcomes, and the experiences of weight management for GDM-related GWG in women with GDM. Methods: This mixed-methods systematic review was retrieved from nine databases. The retrieval time was from the database construction to September 20, 2023, and all studies were published in English and Chinese. The included records used quantitative, qualitative, or mixed methods and reported original studies of weight-related intervention regimens, effects on pregnancy outcomes, and women's experiences and perceptions. This review used a convergent segregated approach to synthesize and integrate research findings from Joanna Briggs Institute (JBI) mixed-methods systematic reviews. Results: There were 16 articles that met the inclusion criteria, and the articles came from seven different countries and included 23,997 women with GDM. The meta-analysis pooled outcomes for the incidence of weight gain exceeding the Institute of Medicine (IOM) recommendations after GDM diagnosis to delivery was 0.31% (95% CI 0.21-0.42). The effectiveness of GDM-related weight interventions in reducing weight gain after GDM diagnosis was supported by quantitative evidence. The GDM-related GWG below the IOM recommendations is a protective factor (OR=0.68, 95%CI 0.48-0.97) for large for gestational Age (LGA), and above the IOM recommendations is a risk factor (OR=1.62, 95%CI 1.15-2.27) for LGA. In addition, no significant statistical significance was found in the pooled outcomes of small for gestational age (SGA). Avoiding excessive weight gain helps to optimize neonatal birth weight, pregnancy outcomes, and maternal blood glucose levels. According to qualitative survey results, some women with GDM experienced weight stigma, and a positive relationship between healthcare providers and GDM women helped in weight management. Conclusion: Following a diagnosis of GDM, weight management interventions positively affected GWG and pregnancy outcomes. In order to improve compliance and safety of weight management in women with GDM, criteria and interventions for weight gain associated with GDM need to be further explored and improved. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=404492, identifier CRD42023404492.

Dose-Response Relationship between Gestational Weight Gain and Neonatal Birthweight in Chinese Women with Excess Weight/Obesity and Gestational Diabetes Mellitus.

Total gestational weight gain (GWG) is identified as a strong and potentially controllable predictor of long-term health outcomes in women with gestational diabetes mellitus (GDM) and infants. When the total GWG of women with excess weight/obesity and GDM does not exceed the Institute of Medicine (IOM) suggested range, neonatal birthweight outcomes may be favorable, but the evidence is limited. Therefore, the objective of this study was to evaluate the dose-response relationship between increased total GWG and the risk of neonatal birthweight in Chinese women with excess weight/obesity and GDM. This study obtained electronic medical records (EMR) from the hospital information system (HIS) of the Chongqing Health Center for Women and Children between July 2017, and June 2020. A retrospective study analyzed the effect of the total GWG of women with excess weight/obesity and GDM on neonatal birthweight. The dose-response relationship between total GWG and neonatal birthweight was studied using a generalized linear model and embedded restricted cubic splines (RCS). The average age of all women with GDM was 31.99 ± 4.47 years, and 27.61% were advanced maternal age (≥35 years). The total GWG among women with excess weight and obesity and GDM greater than the IOM recommendations were found in 42.96% and 58.62% of cases, respectively. Total GWG in women with excess weight and excessing the IOM recommended range is a risk factor for large gestational age (LGA) [adjusted odds ratio (aOR) 0.1.47, 1.08-2.01] and macrosomia (aOR 1.55, 1.04-2.31). In the obesity above group, excessive weight gain increased the risk of LGA (aOR 2.92, 1.33-6.41) and macrosomia (aOR 2.83, 1.03-7.72). We used an RCS to examine pregnant women with excess weight and GDM and discovered a linear dose-response relationship between total GWG and LGA/macrosomia. In women with excess weight and obesity, increases in total GWG above the lowest end of the IOM recommendations range (7 kg and 5 kg) were associated with an increased risk of LGA and macrosomia. Therefore, research is urgently needed to support maternal and newborn health to provide recommendations for the ideal weight increase in women with excess weight/obesity and GDM.

Intranasal delivery of Borneol/R8dGR peptide modified PLGA nanoparticles co-loaded with curcumin and cisplatin alleviate hypoxia in pediatric brainstem glioma which improves the synergistic therapy.

Cisplatin (cis) is a first-line chemotherapeutic used for the treatment of intractable pediatric brainstem glioma (PBSG). Its therapeutic effect in PBSG is, however, critically challenged by the hypoxic microenvironment of the tumor and the presence of the blood brain barrier (BBB). Herein, we report on the intranasal administration of borneol (Bo)/R8dGR peptide modified PLGA based nanoparticles (NP) co-loaded with curcumin and cisplatin (cur/cis). We observed that borneol modification improved the brain penetration of the nanoparticles by reduction of the expression of ZO-1 and occludin in nasal mucosa, while the R8dGR peptide modification allowed the targeting of the NP through the binding on integrin αvß3 receptors which are present on PBSG cells. Following intranasal administration, BoR-cur/cis-NP attenuated hypoxia in the PBSG microenvironment and reduced angiogenesis, which prolonged survival of GL261-bearing PBSG mice. Therefore, intranasal administration of BoR-cur/cis-NP, which deeply penetrate PBSG, is an encouraging strategy to attenuate hypoxia which potentiates the efficacy of cisplatin in the treatment of PBSG.

Nose to brain delivery of Astragaloside IV by ß-Asarone modified chitosan nanoparticles for multiple sclerosis therapy.

Multiple sclerosis (MS), an autoimmune disease, has been considered an inflammatory disorder of the central nervous system (CNS) with demyelination and axonal damage. Although there are certain first-line therapies to treat MS, their unsatisfactory efficacy is partly due to the limited CNS access after systemic administration. Besides, there is an urgent need to treat MS by enhancing remyelination or neuroprotection, or dampen the activity of microglia. Astragaloside IV (ASI) bears anti-inflammatory, antioxidant, remyelination and neuroprotective activity. While its poor permeability, relatively high molecular weight and low lipophilicity restrict it to reach the brain. Therefore, ß-asarone modified ASI loaded chitosan nanoparticles (ASI-ßCS-NP) were prepared to enhance the nose-to-brain delivery and therapeutic effects of ASI on EAE mice. The prepared ASI-ßCS-NP showed mean size of about 120 nm, and zeta potential from +19 to +25 mV. DiR-ßCS-NP was confirmed with good nose-to-brain targeting ability. After intranasal administration, the ASI-ßCS-NP significantly reduced behavioral scores, decreased weight loss, suppressed inflammatory infiltration and astrocyte/microglial activation, reduced demyelination and increased remyelination on a mice EAE model. Our findings indicate that ASI-ßCS-NP may be a potent treatment for MS after nose-to-brain drug delivery.

Natural Products for the Immunotherapy of Glioma.

Glioma immunotherapy has attracted increasing attention since the immune system plays a vital role in suppressing tumor growth. Immunotherapy strategies are already being tested in clinical trials, such as immune checkpoint inhibitors (ICIs), vaccines, chimeric antigen receptor T-cell (CAR-T cell) therapy, and virus therapy. However, the clinical application of these immunotherapies is limited due to their tremendous side effects and slight efficacy caused by glioma heterogeneity, antigen escape, and the presence of glioma immunosuppressive microenvironment (GIME). Natural products have emerged as a promising and safe strategy for glioma therapy since most of them possess excellent antitumor effects and immunoregulatory properties by reversing GIME. This review summarizes the status of current immunotherapy strategies for glioma, including their obstacles. Then we discuss the recent advancement of natural products for glioma immunotherapy. Additionally, perspectives on the challenges and opportunities of natural compounds for modulating the glioma microenvironment are also illustrated.

Puerperium experience and lifestyle in women with gestational diabetes mellitus and overweight/obesity in China: A qualitative study.

Introduction: Women with overweight or obesity and gestational diabetes mellitus (GDM) are at a high risk of developing type 2 diabetes mellitus (T2DM) and other metabolic diseases. Healthy postpartum lifestyles in women with GDM are important for effectively preventing early T2DM occurrence; however, few studies and guidelines focus in China on this issue. Aims: This qualitative study aimed to understand the puerperium experience and lifestyle of women with overweight/obesity and GDM. Methods: A face-to-face, in-depth, and semi-structured interview was conducted using a hermeneutical phenomenology method to collect data that were analyzed through thematic analysis. Results: Out of 61 recruited women with overweight/obesity and history of GDM, 14 women underwent an interview and provided detailed descriptions of their lifestyle experiences during puerperium. The interview data were used to generate four themes-puerperium dietary behavior, weight perception and "confinement" behavior, family support, disease knowledge, and perceived risk-and nine sub-themes. Conclusion: Unhealthy lifestyles, misconceptions about food, the conflict between physical activity and confinement behavior, a lack of social and family support, and low awareness of disease risk are all common among overweight/obese women with a history of GDM. Thus, we emphasized that healthcare providers should provide continuous preventive care from pregnancy to postpartum and promote long-term health in high-risk populations with a history of GDM associated with overweight/obesity.

Emerging Epigenetic-Based Nanotechnology for Cancer Therapy: Modulating the Tumor Microenvironment.

Dysregulated epigenetic modifications dynamically drive the abnormal transcription process to affect the tumor microenvironment; thus, promoting cancer progression, drug resistance, and metastasis. Nowadays, therapies targeting epigenetic dysregulation of tumor cells and immune cells in the tumor microenvironment appear to be promising adjuncts to other cancer therapies. However, the clinical results of combination therapies containing epigenetic agents are disappointing due to systemic toxicities and limited curative effects. Here, the role of epigenetic processes, including DNA methylation, post-translational modification of histones, and noncoding RNAs is discussed, followed by detailed descriptions of epigenetic regulation of the tumor microenvironment, as well as the application of epigenetic modulators in antitumor therapy, with an emphasis on the epigenetic-based advanced drug delivery system in targeting the tumor microenvironment.

Clinical nurses' moral courage and related factors: an empowerment perspective.

BACKGROUND: Moral courage as part of the moral competence of nurses has received increasing attention. Determination of the factors affecting moral courage is important in improving the quality of care. The purpose of this study was to investigate moral courage and related factors among frontline nurses from an empowerment perspective. METHODS: A cross-sectional study was conducted using data collection instruments comprising four main parts: the self-designed form of demographic characteristics, Conditions for Work Effectiveness II (CWEQ-II), Spreitzer's Psychological Empowerment Scale (PES) and Nurses' Moral Courage Scale (NMCS). Data were collected from 226 nurses in a tertiary hospital between February and March 2022 in Wuhan, the capital city of Hubei Province in central China. Descriptive statistics and multiple linear regression were used to analyze the data. RESULTS: The means of the total scores for the CWEQ-II, PES and the NMCS were 3.52 (SD = 0.69), 3.85 (SD = 0.53) and 3.90 (SD = 0.67), respectively. All the dimensions and the total scores of the CWEQ-II and PES were significantly correlated with the NMCS (p < 0.001). According to the multivariate stepwise regression analysis, CWEQ-II and PES were determined to be factors affecting NMCS. These variables explained 35.9% of the total variance in the moral courage scores of nurses. CONCLUSION: The level of moral courage among nurses is above average. Structural empowerment and psychological empowerment were the key factors affecting the promotion of moral courage. Hospital and organizational administrations should be conscious of the role of attach structural empowerment and psychological empowerment in the nursing workplace in increasing moral courage.

The Role of CD4+ T Cells in the Immunotherapy of Brain Disease by Secreting Different Cytokines.

Upon different stimulation, naïve CD4+ T cells differentiate into various subsets of T helper (Th) cells, including Th1, Th2, Th17, and Tregs. They play both protective and pathogenic roles in the central nervous system (CNS) by secreting different cytokines. Failure of the homeostasis of the subgroups in the CNS can result in different brain diseases. Recently, immunotherapy has drawn more and more attention in the therapy of various brain diseases. Here, we describe the role of different CD4+ T cell subsets and their secreted cytokines in various brain diseases, as well as the ways in which by affecting CD4+ T cells in therapy of the CNS diseases. Understanding the role of CD4+ T cells and their secreted cytokines in the immunotherapy of brain disease will provide new targets and therapeutics for the treatment of brain disease. The role of CD4 + T cell subtypes in different diseases and their associated regulatory genes, proteins, and enzymes. CD4 + T cell subtypes play both protective (green) and pathogenic (red) roles in different brain diseases. The immune regulatory effects of CD4 + T cells and their subtypes are promoted or inhibited by different genes, proteins, and enzymes.

Using Nanosphere Embedding to Probe the Surface and Bulk Relaxation in Vitrimers.

The relaxation behavior of vitrimers that is dominated by chemical exchange reactions plays a critical role in vitrimer processing and applications such as self-healing, welding, and others involving the dynamic nature of the vitrimers. Here, we use atomic force microscopy to image embedding of gold nanospheres into epoxy-based vitrimers to assess the surface and bulk relaxation in this material. The results show that even at temperatures well below the bulk topology freezing transition temperature, the nanospheres embed into the vitrimers. The activation energy for the relaxation at the surface and in bulk were estimated in the single measurement, and the former is found to be much lower than the latter. The increase in the surface relaxation is attributed to a combination of an acceleration effect on relaxation by network defects and a decrease in the number of intermolecular exchanges at the surface.

Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.

Role of the renin-angiotensin system in NETosis in the coronavirus disease 2019 (COVID-19).

Myocardial infarction and stroke are the leading causes of death in the world. Numerous evidence has confirmed that hypertension promotes thrombosis and induces myocardial infarction and stroke. Recent findings reveal that neutrophil extracellular traps (NETs) are involved in the induction of myocardial infarction and stroke. Meanwhile, patients with severe COVID-19 suffer from complications such as myocardial infarction and stroke with pathological signs of NETs. Due to the extremely low amount of virus detected in the blood and remote organs (e.g., heart, brain and kidney) in a few cases, it is difficult to explain the mechanism by which the virus triggers NETosis, and there may be a different mechanism than in the lung. A large number of studies have found that the renin-angiotensin system regulates the NETosis at multiple levels in patients with COVID-19, such as endocytosis of SARS-COV-2, abnormal angiotensin II levels, neutrophil activation and procoagulant function at multiple levels, which may contribute to the formation of reticular structure and thrombosis. The treatment of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARBs) and neutrophil recruitment and active antagonists helps to regulate blood pressure and reduce the risk of net and thrombosis. The review will explore the possible role of the angiotensin system in the formation of NETs in severe COVID-19.

Experimental murine models of brainstem gliomas.

As an intractable central nervous system (CNS) tumor, brainstem glioma (BG) is one of the leading causes of pediatric death by brain tumors. Owing to the risk of surgical resection and the little improvement in survival time after radiotherapy and chemotherapy, there is an urgent need to find reliable model systems to better understand the regional pathogenesis of the brainstem and improve treatment strategies. In this review, we outline the evolution of BG murine models, and discuss both their advantages and limitations in drug discovery.

Traditional herbal medicine and nanomedicine: Converging disciplines to improve therapeutic efficacy and human health.

Traditional herbal medicine (THM), an ancient science, is a gift from nature. For thousands of years, it has helped humans fight diseases and protect life, health, and reproduction. Nanomedicine, a newer discipline has evolved from exploitation of the unique nanoscale morphology and is widely used in diagnosis, imaging, drug delivery, and other biomedical fields. Although THM and nanomedicine differ greatly in time span and discipline dimensions, they are closely related and are even evolving toward integration and convergence. This review begins with the history and latest research progress of THM and nanomedicine, expounding their respective developmental trajectory. It then discusses the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of THM on the in vivo fate of nanoparticles. Finally, future development trends, challenges, and research directions are discussed.

Improved Anti-Triple Negative Breast Cancer Effects of Docetaxel by RGD-Modified Lipid-Core Micelles.

PURPOSE: A novel RGD-modified PEGylated lipid-core micelle delivery system was designed to improve the anti-cancer effect of docetaxel on triple negative breast cancer (TNBC). METHODS: The tumor-targeted lipid-core micelles loaded with docetaxel were prepared and characterized. Their morphology, particle size, zeta potential, entrapment efficiency, release profiles, and targeting effects were studied. The antitumor effects of the docetaxel-loaded nano-micelles were investigated in a MDA-MB-231 cell model in vitro and a MDA-MB-231 xenograft model in vivo. RESULTS: The prepared RGD-modified docetaxel-loaded lipid-core micelles were spherical with a particle size of 16.44±1.35 nm, zeta potential of -19.24±1.24 mV, and an encapsulation efficiency of 96.52±0.43%. The drug delivery system showed sustained release properties and could significantly enhance docetaxel uptake by MDA-MB-231 tumor cells in vitro, which was proved to be a caveolae pathway mediated process requiring ATP, Golgi apparatus, and acid lysosomes. The results of the pharmacokinetic study displayed that the area under the curve of the targeted micelles was 3.2-times higher than that of docetaxel commercial injections. Furthermore, in a MDA-MB-231 tumor-bearing mice model, a higher antitumor efficacy than docetaxel commercial injections was displayed, and the safety experiments showed that the micellar material did not cause major organ damage after intravenous administration in mice. CONCLUSION: The novel RGD-modified PEGylated lipid-core micelle delivery system significantly improved the antitumor effects and reduced the side-effects of docetaxel, providing a promising therapeutics for the treatment of TNBC.