Multi-targeted nanoarrays for early broad-spectrum detection of lung cancer based on blood biopsy of tumor exosomes.

Liquid biopsies utilizing tumor exosomes offer a noninvasive approach for cancer diagnosis. However, validation studies consistently report that in the early stages of cancer, the secretion of exosomes by cancer cells is relatively low, while bodily fluids exhibit a high abundance of other interfering biomolecules. Additionally, target mutations or differences in biomarker expression among various lung cancer subtypes may contribute to detection failures. In this study, we propose a targeted nanoarray-based early cancer diagnostic approach for multiple subtypes of lung cancer. The targeted nanoarray was constructed by modifying five targeting aptamers onto mesoporous silica nanoparticles through the conjugation between amino and carboxyl groups. The flow cytometry experiments demonstrated the specific recognition ability of the targeted nanoarray to tumor exosomes in PBS, even at biomarker expression levels as low as 1.5 %. Moreover, the TEM results indicated that the targeted nanoarray could isolate tumor exosomes in the blood of tumor-bearing mice. Furthermore, the targeted nanoarray could detect tumor exosomes in the blood of various lung cancer bearing mice, including at the early stages of cancer, which has just been established for 7 days. Overall, the targeted nanoarray represents a promising tool for the early detection of various subtypes of lung cancer.

Fuyuan decoction prevents nasopharyngeal carcinoma metastasis by inhibiting circulating tumor cells/ endothelial cells interplay and enhancing anti-cancer immune response.

Distant metastasis is a major cause of treatment failure in cancer patients and a key challenge to improving cancer care today. We hypothesized that enhancing anti-cancer immune response and inhibiting circulating tumor cells (CTCs) adhesion and transendothelial migration through synergistic multi-target approaches may effectively prevent cancer metastasis. "Fuyuan Decoction" (FYD) is a traditional Chinese medicine compound that is widely used to prevent postoperative metastasis in cancer patients, but its underlying mechanism remains unclear. In this work, we systematically elucidated the underlying molecular mechanism by which FYD prevents cancer metastasis through multi-compound and multi-target synergies in vitro and in vivo. FYD significantly prevented cancer metastasis at non-cytotoxic concentrations by suppressing the adhesion of CTCs to endothelial cells and their subsequent transendothelial migration, as well as enhancing anti-cancer immune response. Mechanistically, FYD interrupts adhesion of CTCs to vascular endothelium by inhibiting TNF-α-induced CAMs expression via regulation of the NF-κB signaling pathway in endothelial cells. FYD inhibits invasion and migration of CTCs by suppressing EMT, PI3K/AKT and FAK signaling pathways. Moreover, FYD enhances the anti-cancer immune response by significantly increasing the population of Tc and NK cells in the peripheral immune system. In addition, the chemical composition of FYD was determined by UPLC-HRMS, and the results indicated that multiple compounds in FYD prevents cancer metastasis through multi-target synergistic treatment. This study provides a modern medical basis for the application of FYD in the prevention of cancer metastasis, and suggesting that multi-drug and multi-target synergistic therapy may be one of the most effective ways to prevent cancer metastasis.

Advancements in the synthesis of carbon dots and their application in biomedicine.

As a sort of fluorescent carbon nanomaterial with a particle size of less than 10 nm, carbon dots (CDs) have their own merits of good dispersibility in water, stable optical properties, strong chemical inertness, stable optical properties, and good biosecurity. These excellent peculiarities facilitated them like sensing, imaging, medicine, catalysis, and optoelectronics, making them a new star in the field of nanotechnology. In particular, the development of CDs in the fields of chemical probes, imaging, cancer therapy, antibacterial and drug delivery has become a hot topic in current research. Although the biomedical applications in CDs have been demonstrated in many research articles, a systematic summary of their role in biomedical applications is scarce. In this review, we introduced the basic information of CDs in detail, including synthesis approaches of CDs as well as their favorable properties including photoluminescence and low cytotoxicity. Subsequently, the application of CDs in the field of biomedicine was emphasized. Finally, the main challenges and research prospects of CDs in this field were proposed, which might provide some detailed information in designing new CDs in this promising biomedical field.

Biochar's dual role in greenhouse gas emissions: Nitrogen fertilization dependency and mitigation potential.

Biochar was popularly used for reducing greenhouse gas (GHG) emissions in vegetable production, but using biochar does not necessarily guarantee a reduction in GHG emissions. Herein, it's meaningful to elucidate the intricate interplay among biochar properties, soil characteristics, and GHG emissions in vegetable production to provide valuable insights for informed and effective mitigation strategies. Therefore, in current research, a meta-analysis of 43 publications was employed to address these issues. The boost-regression analysis results indicated that the performance of biochar in inhibiting N2O emissions was most affected by the N application rate both in high and low N application conditions. Besides, biochar had dual roles and showed well performance in reducing GHG emissions under low N input (≤300 kg N ha-1), while having the opposite effect during high N input (>300 kg N ha-1). Specifically, applying biochar under low N fertilization input could obviously reduce soil N2O emissions, CO2 emissions, and CH4 emissions by 18.7 %, 17.9 %, and 16.9 %, respectively. However, the biochar application under high N fertilization input significantly (P < 0.05) increased soil N2O emissions, CO2 emissions, and CH4 emissions by 39.7 %, 43.0 %, and 27.7 %, respectively. Except for the N application rate, the soil pH, SOC, biochar C/N ratio, biochar pH, and biochar pyrolysis temperature are also the key factors affecting the control of GHG emissions in biochar-amended soils. The findings of this study will contribute to deeper insights into the potential application of biochar in regulating GHG under consideration of N input, offering scientific evidence and guidance for sustainable agriculture management.

Multifunctional metal-coordinated Co-assembled carrier-free nanoplatform based on dual-drugs for ferroptosis-mediated cocktail therapy of hepatocellular carcinoma growth and metastasis.

The heterogeneity of hepatocellular carcinoma (HCC) and the complexity of the tumor microenvironment (TME) pose challenges to efficient drug delivery and the antitumor efficacy of combined or synergistic therapies. Herein, a metal-coordinated carrier-free nanodrug (named as USFe3+ LA NPs) was developed for ferroptosis-mediated multimodal synergistic anti-HCC. Natural product ursolic acid (UA) was incorporated to enhance the sensitivity of tumor cells to sorafenib (SRF). Surface decoration of cell penetration peptide and epithelial cell adhesion molecule aptamer facilitated the uptake of USFe3+ LA NPs by HepG2 cells. Meanwhile, Fe3+ ions could react with intracellular hydrogen peroxide, generating toxic hydroxyl radical (·OH) for chemodynamical therapy (CDT) and amplified ferroptosis by cystine/glutamate antiporter system (System Xc-), which promoted the consumption of glutathione (GSH) and inhibited the expression of glutathione peroxidase 4 (GPX4). Notably, these all-in-one nanodrugs could inhibit tumor metastasis and induced immunogenic cell death (ICD). Last but not least, the nanodrugs demonstrated favorable biocompatibility, augmenting the immune response against the programmed death-ligand 1 (PD-L1) by increasing cytotoxic T cell infiltration. In vivo studies revealed significant suppression of tumor growth and distant metastasis. Overall, our work introduced a novel strategy for applications of metal-coordinated co-assembled carrier-free nano-delivery system in HCC combination therapy, especially in the realms of cancer metastasis prevention and immunotherapy.

Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade.

Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated individually, their combined use and the potential for a synergistic or augmented effect remain unexplored. This study aims to investigate the effect of curcumin (Cur) and resveratrol (Res) as a potential combination therapy on MAFLD. Cur, Res and Cur+Res were tested in palmitic acid (PA)-induced-HepG2 cells. MAFLD model was established using Goto-Kakizaki rats. The animals were treated with vehicle control (model group), Cur (150 mg/kg), Res (150 mg/kg), Cur+Res (150 mg/kg, 8:2, w/w), or metformin (Met, positive control, 400 mg/kg/day) via oral gavage for 4 weeks. Wistar rats were used as the control group. Network pharmacology was conducted to elucidate the molecular actions of Cur and Res, followed by q-PCR and immunoblotting in vivo. Cur+Res exhibited synergistic effects in reducing triglyceride, total cholesterol and lipid accumulation in PA-induced HepG2 cells. The combination also markedly attenuated hepatic steatosis in the MAFLD rats. Network pharmacology illustrated that the interaction of Cur and Res was associated with the modulation of multiple molecular targets associated with the PI3K/AKT/mTOR and HIF-1 signaling pathways. Experimental results confirmed that Cur+Res nomalised the gene targets and protein expressions in the PI3K/AKT/mTOR and HIF-1 signaling pathways, including PI3K, mTOR, STAT-3, HIF-1α, and VEGF. The present study demonstrated an advanced effect of Cur and Res in combination to attenuate MAFLD, and the mechanism is at least partly associated with the modulation of the PI3K/AKT/mTOR and HIF-1 signaling pathways.

Ten years' trend analysis for Taiwanese youth high school students' health behaviors.

PURPOSE: To delineate the 10 years' trend regarding Taiwanese adolescents' health perspectives and compare the differences of six adolescent health aspects between Taiwan and the U.S. METHODS: The anonymous structured questionnaire was done every other year with representative sampling methods as Youth Risk Behavior Surveillance System in the United States. Twenty-one questions from six health aspects were extracted for further analysis. Multivariate regression analysis was performed to delineate the relationship among protective factors and risk-taking behaviors, respectively. RESULTS: Overall, 22,419 adolescents were recruited. There were decreasing trend in terms of risk-taking behaviors, such as early contact to pornography (< age 16) (70.6%-60.9%), early cigarette use (< age 13) (20.7%-14.0%), and seriously considering suicide (36.0%-17.8%). There was an increasing trend in behaviors harmful to health: current alcohol drinkers (18.9%-23.4%), and staying up late every day (15.2%-18.5%). Multivariate regression analysis after adjusting gender and grade; it disclosed an increasing trend in protective assets, such as having multiple intimate friends (75.8%-79.3%), satisfaction to body weight and body shape (31.5%-36.1% and 34.5%-40.7%), as well as always wearing a helmet while riding a bike (1.8%-3.0%). CONCLUSION: We should continuously monitor the health status trend of the adolescents to provide them with a healthier environment and well-being.

Ganoderma lucidum extract promotes tumor cell pyroptosis and inhibits metastasis in breast cancer.

Regulation of tumor cell death is a fundamental mechanism for tumor treatment. However, most tumors are resistant to cell death. Triggering inflammatory cell death, pyroptosis, may provide a new view of enhancing tumor cell death. Here we report a new role of Ganoderma lucidum extract (GLE) in pyroptotic cell death. Treatment with GLE (50-200 µg/mL) significantly elevated reactive oxygen species (ROS) levels and caused pyroptotic cell death in breast cancer cells. Mechanistically, GLE activates caspase 3 and further cleaves the gasdermin E (GSDME) protein to form pores on the cell membrane, releasing massive amounts of inflammatory factors in breast cancer cells. We also showed that GLE enhanced antitumor immune responses by substantially increasing the subsets of natural killer (NK) and CD8+T cells in the peripheral immune system and tumor microenvironment. In addition, GLE destroys multiple steps of tumor metastasis, including adhesion, migration, invasion, colonization, and angiogenesis. Collectively, these results suggest that GLE provides a potential approach for breast cancer treatment, which may complement chemotherapy or immunotherapy for cancer metastasis.

Combination of Se-methylselenocysteine, D-α-tocopheryl succinate, ß-carotene, and L-lysine can prevent cancer metastases using as an adjuvant therapy.

OBJECTIVES: Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-|α|-tocopheryl succinic acid (VES), ß|-carotene (ß|-Ca), and L-lysine (Lys). METHODS: The effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo. RESULTS: MVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function. CONCLUSIONS: This study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.

Cancer metastasis chemoprevention prevents circulating tumour cells from germination.

The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law. The cancer crusade costs trillions with disappointing returns, teasing the possibility of a new breakthrough. Cure for cancer post-metastases still seems tantalisingly out of reach. Once metastasized, cancer-related death is extremely difficult, if not impossible, to be reversed. Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells (CTCs) from initiating metastases safely and effectively, and is disparate from the traditional cancer chemotherapy and cancer chemoprevention. Deep learning of the biology of CTCs and their disseminating organotropism, complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche (the first and the most important part in cancer metastatic cascade) can be pharmaceutically interrupted, the lethal metastatic cascade could be prevented from getting initiated. We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination, provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites. The adhesion/inhibition ratio (AIR) is defined for selecting the best cancer metastasis chemopreventive candidates. The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.

Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration.

Metastasis is the leading cause of cancer-related death and a critical challenge in improving cancer treatment today. Circulating tumor cells (CTCs) adhesion to and across the vascular endothelium are critical steps in the establishment of micrometastatic foci away from the primary tumor. Therefore, we believe that interrupting CTCs adhesion to endothelium and transendothelial migration may efficiently prevent cancer metastasis. Fucoxanthin (Fx) is an algal carotenoid widely distributed in brown algae, macroalgae, and diatoms. Previous studies have found that Fx has various pharmacological activities, including antidiabetic, antioxidant, anti-inflammatory, anti-obesity, antimalarial, anticancer, and so on. However, it remains unclear whether Fx has a preventive effect on cancer metastasis. Here, we found that Fx interrupts breast cancer cells MCF-7 adhesion to endothelium and transendothelial migration, thus inhibiting CTCs-based pulmonary metastasis in vivo. The hetero-adhesion assay showed that Fx significantly inhibited the expression of inflammatory factor-induced cell adhesion molecules (CAMs) and the resulting adhesion between MCF-7 cells and endothelial cells. The wound-healing and transwell assays showed that Fx significantly inhibited the motility, invasion, and transendothelial migration abilities of MCF-7 cells. However, the same concentration of Fx did not significantly alter the cell viability, cell cycle, apoptosis, and ROS of breast cancer cells, thus excluding the possibility that Fx inhibits MCF-7 cell adhesion and transendothelial migration through cytotoxicity. Mechanistically, Fx inhibits the expression of CAMs on endothelial cells by inhibiting the NF-кB signaling pathway by down-regulating the phosphorylation level of IKK-α/ß, IкB-α, and NF-кB p65. Fx inhibits transendothelial migration of MCF-7 cells by inhibiting Epithelial-to-mesenchymal transition (EMT), PI3K/AKT, and FAK/Paxillin signaling pathways. Moreover, we demonstrated that Fx significantly inhibits the formation of lung micrometastatic foci in immunocompetent syngeneic mouse breast cancer metastasis models. We also showed that Fx enhances antitumor immune responses by substantially increasing the subsets of cytotoxic T lymphocytes in the peripheral immune system. This new finding provides a basis for the application of Fx in cancer metastatic chemoprevention and suggests that interruption of the CTCs adhesion to endothelium and transendothelial migration may serve as a new avenue for cancer metastatic chemoprevention.

Comparative Analysis of Phytochemical Profiles and Antioxidant Activities between Sweet and Sour Wampee (Clausena lansium) Fruits.

As a local medicine and food, wampee fruit, with abundant bioactive compounds, is loved by local residents in Southern China. Titratable acid (TA), total sugar (TS), and total phenolic and flavonoid contents were detected, and phytochemical profiles and cellular antioxidant activities were analyzed by the HPLC and CAA (cellular antioxidant activity) assay in five sweet wampee varieties and five sour wampee varieties. Results showed that the average TS/TA ratio of sweet wampee varieties was 29 times higher than sour wampee varieties, while TA content was 19 times lower than sour wampee varieties. There were much lower levels of total phenolics, flavonoids, and antioxidant activities in sweet wampee varieties than those in sour wampee varieties. Eight phytochemicals were detected in sour wampee varieties, including syringin, rutin, benzoic acid, 2-methoxycinnamic acid, kaempferol, hesperetin, nobiletin, and tangeretin, while just four of them were detected in sweet wampee varieties. Syringin was the only one that was detected in all the sour wampee varieties and was not detected in all sweet wampee varieties. Correlation analysis showed significant positive correlations between TA with phenolics, flavonoids, and total and cellular (PBS wash) antioxidant activities, while there were significant negative correlations between TS/TA with phenolic and cellular (no PBS wash) antioxidant activities. This suggested that the content of titratable acid in wampee fruit might have some relationship with the contents of phenolics and flavonoids. Sour wampee varieties should be paid much attention by breeders for their high phytochemical contents and antioxidant activities for cultivating germplasms with high health care efficacy.

Similarities and differences between embryonic implantation and CTC invasion: Exploring the roles of abortifacients in cancer metastasis chemoprevention.

Mifepristone (RU486) is a chemical contraceptive marketed in more than 55 countries and used by hundreds of millions of women worldwide. Current studies reported its uses by both genders for a safe and long-term psychotic depression and particularly for traditional cancer chemotherapy. Here, we investigated the multidisciplinary data from recent large epidemiological chemoprevention studies for long-term use of oral contraceptives to reduce cancer risk, and from the unsuccessful clinical trials of mifepristone used as a post-metastatic anticancer drug, and elucidated the similarities and differences in cellular and molecular processes between embryonic implantation to endometrium and adhesion/invasion of circulating tumor cells (CTCs) to vascular endothelium. The deep analyses provide a stronger scientific basis for repurposing abortifacients for safe and effective cancer metastatic chemoprevention. Initiation of such cancer drug development strategy represents a paradigm shift from traditional post-metastasis treatments to novel pre-metastasis chemoprevention.

Protein Kinase C-Mediated Hyperphosphorylation and Lateralization of Connexin 43 Are Involved in Autoimmune Myocarditis-Induced Prolongation of QRS Complex.

Myocarditis is a serious and potentially life-threatening disease, which leads to cardiac dysfunction and sudden cardiac death. An increasing number of evidence suggests that myocarditis is also a malignant complication of coronavirus pneumonia, associated with heart failure and sudden cardiac death. Prolonged QRS complexes that are related to malignant arrhythmias caused by myocarditis significantly increase the risk of sudden cardiac death in patients. However, the molecular mechanisms are not fully known at present. In this study, we identify protein kinase C (PKC) as a new regulator of the QRS complex. In isolated hearts of normal rats, the PKC agonist, phorbol-12-myristate-13-acetate (PMA), induced prolongation of the QRS complex. Mechanistically, hyperphosphorylation and lateralization of connexin 43 (Cx43) by PKC induced depolymerization and internalization of Cx43 gap junction channels and prolongation of the QRS duration. Conversely, administration of the PKC inhibitor, Ro-32-0432, in experimental autoimmune myocarditis (EAM) rats after the most severe inflammation period still significantly rescued the stability of the Cx43 gap junction and alleviated prolongation of the QRS complex. Ro-32-0432 reduced phosphorylation and blocked translocation of Cx43 in EAM rat heart but did not regulate the mRNA expression level of ventricular ion channels and the other regulatory proteins, which indicates that the inhibition of PKC might have no protective effect on ion channels that generate ventricular action potential in EAM rats. These results suggest that the pharmacological inhibition of PKC ameliorates the prolongation of the QRS complex via suppression of Cx43 hyperphosphorylation, lateralization, and depolymerization of Cx43 gap junction channels in EAM rats, which provides a potential therapeutic strategy for myocarditis-induced arrhythmias.

Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention.

BACKGROUND: The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. METHODS: Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17ß-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. RESULTS: Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17ß-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. CONCLUSIONS: The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.

Tumor-derived Exosome Promotes Metastasis via Altering its Phenotype and Inclusions.

Although tumor-derived exosomes play an important role in the process of metastasis, differences in exosomes secreted by the same cells at different stages or conditions have not been noticed by most of the relevant researchers. Here we developed a lung cancer model in nude mice, and the phenotype and inclusions of exosomes secreted by early and advanced tumors were analysed. The size distribution and surface topography of these two exosomes were not significantly different, but the expression of CD63 in early tumor exosome (E-exosome) was significantly lower than that in advanced tumor exosome (A-exosome). α-SMA expression on HELF cells treated with A-exosome was significantly higher than that treated with E-exosome. The ability of A-exosome to promote the migration of A549 cells was better than E-exosome. Furthermore, small RNA sequence showed that only 3 of the 171 detected-small RNAs were expressed simultaneously in both exosomes. These findings proved that there are significant differences in inclusions and functions between the early and late exosomes of the same tumor. The study highlights the importance of exosomes in cancer metastasis, and might suggest exosomes can be used as biomarkers and therapeutic targets for cancer metastasis.

Tumor-derived exosomes can specifically prevent cancer metastatic organotropism.

Each type of cancer has its own specific metastatic route developed by disseminating circulating tumor cells (CTCs) and related extracellular vesicles to the target organ, i.e., metastasis organotropism. Tumor-derived small extracellular vesicles (herein exosomes, EXO) play an important role in determining cancer organotropic metastases to pre-metastasis niches. We therefore hypothesized that drug-loaded EXO may mix well with their companion small extracellular vesicles to specifically target the aimed metastatic organ via organotropism. Here, we demonstrate that the circulating breast-cancer-derived EXO loaded with doxorubicin (EXO-DOX) can mingled with their original companion EXO and inhibit breast cancer metastasis to lungs. The CD47 on the EXO-DOX prevented EXO-DOX from immune attack and prolonged their circulation in blood. The tissue distribution ratio of EXO-DOX is identical to the ratio of their companion EXO due to the specific affinity of EXO to integrins in targeted tissues. Quantitative accumulation of EXO-DOX in the mouse lungs is proportional to the organotropism of the circulating breast cancer cells that disseminate from subcutaneously-implanted human breast cancer cells in mice. EXO-DOX inhibited angiogenesis and cancer cell proliferation, resulting in prevention of breast cancer metastasis to the lungs. This study opens a novel path to use Trojan small extracellular vesicles for specifically controlled release of active components by small extracellular vesicles organotropism mechanism to the targeted organ for disease chemoprevention.