Membrane Fusion Liposomes Deliver Antifibrotic and Chemotherapeutic Drugs Sequentially to Enhance Tumor Treatment Efficacy by Reshaping Tumor Microenvironment.

The intricate tumor microenvironment in triple-negative breast cancer (TNBC) hampers chemotherapy and immunotherapy efficacy due to dense extracellular matrix (ECM) by tumor-associated fibroblasts (TAFs). Nanoparticle-based therapies, especially "all-in-one" nanoparticles, have shown great potential in combined drug delivery strategies to reshape the tumor microenvironment and enhance therapeutic efficiency. However, these "all-in-one" nanoparticles suffer from limitations in targeting different target cells, uncontrollable dosing ratio, and disregarding the impact of delivery schedules. This study prepared cell membrane fusion liposomes (TAFsomes and CCMsomes) to load FDA-approved antifibrotic drug pirfenidone (PFD/TAFsomes) and antitumor drug doxorubicin (DOX/CCMsomes). These liposomes can specifically target TAFs cells and tumor cells, and combined administration can effectively inhibit TAFs activity, reshape the tumor microenvironment (TME), and significantly enhance the tumor chemotherapy efficacy. Combined drug delivery defeats "all-in-one" liposomes (DOX/PFD/Liposomes, DOX/PFD/TAFsomes, and DOX/PFD/CCMsomes) by flexibly adjusting the drug delivery ratio. Moreover, an asynchronous delivery strategy that optimizes the administration schedule not only further improves the therapeutic effect, but also amplifies the effectiveness of α-PD-L1 immunotherapy by modulating the tumor immune microenvironment. This delivery strategy provides a personalized treatment approach with clinical translation potential, providing new ideas for enhancing the therapeutic effect against solid tumors such as TNBC.

Selective Elimination of Senescent Cancer Cells by Galacto-Modified PROTACs.

Although the selective and effective clearance of senescent cancer cells can improve cancer treatment, their development is confronted by many challenges. As part of efforts designed to overcome these problems, prodrugs, whose design is based on senescence-associated ß-galactosidase (SA-ß-gal), have been developed to selectively eliminate senescent cells. However, chemotherapies relying on targeted molecular inhibitors as senolytic drugs can induce drug resistance. In the current investigation, we devised a new strategy for selective degradation of target proteins in senescent cancer cells that utilizes a prodrug composed of the SA-ß-gal substrate galactose (galacto) and the proteolysis-targeting chimeras (PROTACs) as senolytic agents. Prodrugs Gal-ARV-771 and Gal-MS99 were found to display senolytic indexes higher than those of ARV-771 and MS99. Significantly, results of in vivo studies utilizing a human lung A549 xenograft mouse model demonstrated that concomitant treatment with etoposide and Gal-ARV-771 leads to a significant inhibition of tumor growth without eliciting significant toxicity.

Cholesterol-modified sphingomyelin chimeric lipid bilayer for improved therapeutic delivery.

Cholesterol (Chol) fortifies packing and reduces fluidity and permeability of the lipid bilayer in vesicles (liposomes)-mediated drug delivery. However, under the physiological environment, Chol is rapidly extracted from the lipid bilayer by biomembranes, which jeopardizes membrane stability and results in premature leakage for delivered payloads, yielding suboptimal clinic efficacy. Herein, we report a Chol-modified sphingomyelin (SM) lipid bilayer via covalently conjugating Chol to SM (SM-Chol), which retains membrane condensing ability of Chol. Systemic structure activity relationship screening demonstrates that SM-Chol with a disulfide bond and longer linker outperforms other counterparts and conventional phospholipids/Chol mixture systems on blocking Chol transfer and payload leakage, increases maximum tolerated dose of vincristine while reducing systemic toxicities, improves pharmacokinetics and tumor delivery efficiency, and enhances antitumor efficacy in SU-DHL-4 diffuse large B-cell lymphoma xenograft model in female mice. Furthermore, SM-Chol improves therapeutic delivery of structurally diversified therapeutic agents (irinotecan, doxorubicin, dexamethasone) or siRNA targeting multi-drug resistant gene (p-glycoprotein) in late-stage metastatic orthotopic KPC-Luc pancreas cancer, 4T1-Luc2 triple negative breast cancer, lung inflammation, and CT26 colorectal cancer animal models in female mice compared to respective FDA-approved nanotherapeutics or lipid compositions. Thus, SM-Chol represents a promising platform for universal and improved drug delivery.

Camptothesome-based combination nanotherapeutic regimen for improved colorectal cancer immunochemotherapy.

Camptothesome is a sphingomyelin-conjugated camptothecin (SM-CSS-CPT) nanovesicle that fortified the therapeutic delivery of CPT in diverse cancer types. To mitigate the Camptothesome-induced IDO1 negative feedback mechanism, we had co-encapsulated, indoximod (IND, IDO1 inhibitor) into Camptothesome using doxorubicin-derived IND (DOX-IND). To maximize the therapeutic potential of DOX-IND/Camptothesome, herein, we first dissected the synergistic drug ratio (DOX-IND/SM-CSS-CPT) via systematical in vitro screening. DOX-IND/Camptothesome with optimal drug ratio synchronized in vivo drug delivery with significantly higher tumor uptake compared to free drugs. This optimum DOX-IND/Camptothesome outperformed the combination of Camptothesome, Doxil and IND or other IDO1 inhibitors (BMS-986205 or epacadostat) in treating mice bearing late-stage MC38 tumors, and combination with immune checkpoint blockade (ICB) enabled it to eradicate 60 % of large tumors. Further, this optimized co-delivery Camptothesome beat Folfox and Folfiri, two first-line combination chemotherapies for colorectal cancer in antitumor efficacy and exhibited no side effects as compared to the severe systemic toxicities associated with Folfox and Folfiri. Finally, we demonstrated that the synergistic DOX-IND/Camptothesome was superior to the combined use of Onivyde + Doxil + IND in curbing the advanced orthotopic CT26-Luc tumors and eliminated 40 % tumors with complete metastasis remission when cooperated with ICB, eliciting stronger anti-CRC immune responses and greater reversal of immunosuppression. These results corroborated that with precise optimal synergistic drug ratio, the therapeutic potential of DOX-IND/Camptothesome can be fully unleased, which warrants further clinical investigation to benefit the cancer patients.

Sphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy.

Epacadostat (EPA), the most advanced IDO1 inhibitor, in combination with PD-1 checkpoint inhibitor, has failed in a recent Phase III clinical trial for treating metastatic melanoma. Here we report an EPA nanovesicle therapeutic platform (Epacasome) based on chemically attaching EPA to sphingomyelin via an oxime-ester bond highly responsive to hydrolase cleavage. Via clathrin-mediated endocytosis, Epacasome displays higher cellular uptake and enhances IDO1 inhibition and T cell proliferation compared to free EPA. Epacasome shows improved pharmacokinetics and tumour accumulation with efficient intratumoural drug release and deep tumour penetration. Additionally, it outperforms free EPA for anticancer efficacy, potentiating PD-1 blockade with boosted cytotoxic T lymphocytes (CTLs) and reduced regulatory T cells and myeloid-derived suppressor cells responses in a B16-F10 melanoma model in female mice. By co-encapsulating immunogenic dacarbazine, Epacasome further enhances anti-tumor effects and immune responses through the upregulation of NKG2D-mediated CTLs and natural killer cells responses particularly when combined with the PD-1 inhibitor in the late-stage metastatic B16-F10-Luc2 model in female mice. Furthermore, this combination prevents tumour recurrence and prolongs mouse survival in a clinically relevant, post-surgical melanoma model in female mice. Epacasome demonstrates potential to synergize with PD-1 blockade for improved response to melanoma immunotherapy.

Optimization of water quality index models using machine learning approaches.

To optimize the water quality index (WQI) assessment model, this study upgraded the parameter weight values and aggregation functions. We determined the combined weights based on machine learning and game theory to improve the accuracy of the models, and proposed new aggregation functions to reduce the uncertainty of the model. A new water quality assessment system was established, and took the Chaobai River Basin as a case study. To optimize the weight, two combined weights were established based on game theory. The weight CWAE was combined by the Analytic Hierarchy Process (AHP) and Entropy Weight Method (EWM). The weight CWAL was combined by AHP and machine learning (LightGBM). CWAL was judged to be an optimal composite weight by comparing the coefficient of variation (CV) values and the Kaiser-Meyer-Olkin (KMO) extracted values. To reduce the uncertainty of the model, we proposed two aggregation functions, the Sinusoidal Weighted Mean (SWM) and the Log-weighted Quadratic Mean (LQM). The three water quality assessment models (WQIS, WQIL and WQIW) were established based on the optimal weights besides. All three models had good reliability. Both WQIS and WQIW models had low eclipsing problems (25.49% and 18.63%). The accuracy of the models was ranked as WQIS > WQIW > WQIL. The uncertainty of WQIs (0.000) in assessing poor water quality was low, and so was WQIW (0.259) in assessing good water quality. Overall, the WQIS model was recommended for assessing poor water quality and the WQIW model was recommended for assessing good water quality. The assessment results of WQIS showed that the Chaobai River Basin was "slightly polluted", and the water quality upstream was better than that downstream. TN was the main pollutant in the basin, and there was slight pollution with CODMn, CODCr, BOD5, etc. There was little metal contamination, only a few months exceeded Class I. The model established in this study can provide a reference for the same type work of water quality assessment. The assessment results can provide a scientific basis for the protection of the regional water environment.

Digital Image Correlation with a Prism Camera and Its Application in Complex Deformation Measurement.

Given the low accuracy of the traditional digital image correlation (DIC) method in complex deformation measurement, a color DIC method is proposed using a prism camera. Compared to the Bayer camera, the Prism camera can capture color images with three channels of real information. In this paper, a prism camera is used to collect color images. Relying on the rich information of three channels, the classic gray image matching algorithm is improved based on the color speckle image. Considering the change of light intensity of three channels before and after deformation, the matching algorithm merging subsets on three channels of a color image is deduced, including integer-pixel matching, sub-pixel matching, and initial value estimation of light intensity. The advantage of this method in measuring nonlinear deformation is verified by numerical simulation. Finally, it is applied to the cylinder compression experiment. This method can also be combined with stereo vision to measure complex shapes by projecting color speckle patterns.

A novel framework to improve the consistency of water quality attribution from natural and anthropogenic factors.

One critical question for water security and sustainable development is how water quality responses to the changes in natural factors and human activities, especially in light of the expected exacerbation in water scarcity. Although machine learning models have shown noticeable advances in water quality attribution analysis, they have limited interpretability in explaining the feature importance with theoretical guarantees of consistency. To fill this gap, this study built a modelling framework that employed the inverse distance weighting method and the extreme gradient boosting model to simulate the water quality at grid scale, and adapted the Shapley additive explanation to interpret the contributions of the drivers to water quality over the Yangtze River basin. Different from previous studies, we calculated the contribution of features to water quality at each grid within river basin and aggregated the contribution from all the grids as the feature importance. Our analysis revealed dramatic changes in response magnitudes of water quality to drivers within river basin. Air temperature had high importance in the variability of key water quality indicators (i.e. ammonia-nitrogen, total phosphorus, and chemical oxygen demand), and dominated the changes of water quality in Yangtze River basin, especially in the upstream region. In the mid- and downstream regions, water quality was mainly affected by human activities. This study provided a modelling framework applicable to robustly identify the feature importance by explaining the contribution of features to water quality at each grid.

Phosphorus - The main limiting factor in riverine ecosystems in China.

River receive substantial nutrient inputs, and serve as the main channel for nitrogen and phosphorus to enter the lake, their nutrient control is of great significance to the alleviation of lake eutrophication. While nutrient limitation affects the primary productivity of water ecosystems and the biodiversity of aquatic communities, identifying the limiting factors in riverine ecosystems across China remains elusive. Here, we explore which nutrients have a stronger effect on nutritional balance and aquatic ecosystems in China's rivers based on the total nitrogen (TN) and total phosphorus (TP) observations from 1412 sampling sites in 2018. This study supports the following three main conclusions. Though the percentages of the sites with TN or TP exceeding the limits varied as per different mesotrophic targets, and TP (53.7 %) contributed more to nutrient enrichment than TN (46.3 %). In addition, the spatial distribution characteristics of river nutrients were high in the north (arid zone) and low in the south (humid zone) in China. According to four classification criteria of N:P ratio, 70.8 % of the sampling sites were attributed to phosphorus limiting, much higher than the sites with nitrogen limiting (4.1 %). TN and TP have a synergistic effect on river nutrients, while TP has a stronger regulation framework. Our results reveal that the nutrients in China's rivers are mainly phosphorus limiting, which implies that phosphorus-oriented best management practices are more likely to maintain the nutrient balance of rivers towards healthy aquatic ecosystems. Synopsis: Phosphorus is the key factor that affecting the stability and nutrient balance of riverine ecosystem.

Nanotechnology-enabled immunogenic cell death for improved cancer immunotherapy.

Tumor immunotherapy has revolutionized the field of oncology treatments in recent years. As one of the promising strategies of cancer immunotherapy, tumor immunogenic cell death (ICD) has shown significant potential for tumor therapy. Nanoparticles are widely used for drug delivery due to their versatile characteristics, such as stability, slow blood elimination, and tumor-targeting ability. To increase the specificity of ICD inducers and improve the efficiency of ICD induction, functionally specific nanoparticles, such as liposomes, nanostructured lipid carriers, micelles, nanodiscs, biomembrane-coated nanoparticles and inorganic nanoparticles have been widely reported as the vehicles to deliver ICD inducers in vivo. In this review, we summarized the strategies of different nanoparticles for ICD-induced cancer immunotherapy, and systematically discussed their advantages and disadvantages as well as provided feasible strategies for solving these problems. We believe that this review will offer some insights into the design of effective nanoparticulate systems for the therapeutic delivery of ICD inducers, thus, promoting the development of ICD-mediated cancer immunotherapy.

Spatiotemporal differences in riverine nitrogen and phosphorus fluxes and associated drivers across China from 1980 to 2018.

Increases in nutrient loadings to waterways over the past four decades have led to widespread eutrophication and water quality impairments across China. Understanding the spatial, interannual and long-term variations in nutrient loadings and associated drivers at the national scale is crucial for developing effective nutrient reduction strategies. However, the controls on, and spatiotemporal variations in, nutrient fluxes remain a problem from both an academic and management perspective. This study provides spatially extensive and temporally contiguous estimates of changes in riverine total nitrogen (TN), ammonia nitrogen (NH3-N) and total phosphorus (TP) fluxes for continental area of China based on machine learning stack models and empirical modeling over the period from 1980 to 2018. Results reveal considerable spatial, interannual and long-term variability in annual TN, NH3-N and TP fluxes, with spatial variations in average TN and NH3-N fluxes primarily driven by net anthropogenic nitrogen inputs. Interannual variability is dominated by precipitation across continental areas of China. Spatial variability in the estimated average annual TP flux in the undeveloped western and the developed middle east regions of China are primarily controlled by net anthropogenic phosphorus inputs and precipitation, respectively. We found that TN, NH3-N and TP fluxes increased from 1980 to 2018 in watersheds in East China; the national mean annual TN, NH3-N and TP fluxes increased before 2015 and decreased after 2015. This study illustrates the important role of precipitation and temperature variability in controlling the spatial, interannual and long-term variability of nutrient fluxes, and indicates that the influence of the meteorological conditions on annual loadings is needed when designing watershed nutrient reduction or management strategies.

Lipid-Based Nanotechnology: Liposome.

Over the past several decades, liposomes have been extensively developed and used for various clinical applications such as in pharmaceutical, cosmetic, and dietetic fields, due to its versatility, biocompatibility, and biodegradability, as well as the ability to enhance the therapeutic index of free drugs. However, some challenges remain unsolved, including liposome premature leakage, manufacturing irreproducibility, and limited translation success. This article reviews various aspects of liposomes, including its advantages, major compositions, and common preparation techniques, and discusses present U.S. FDA-approved, clinical, and preclinical liposomal nanotherapeutics for treating and preventing a variety of human diseases. In addition, we summarize the significance of and challenges in liposome-enabled nanotherapeutic development and hope it provides the fundamental knowledge and concepts about liposomes and their applications and contributions in contemporary pharmaceutical advancement.

Surface-modified nanotherapeutics targeting atherosclerosis.

Atherosclerosis is a chronic and metabolic-related disease that is a serious threat to human health. Currently available diagnostic and therapeutic measures for atherosclerosis lack adequate efficiency which requires promising alternative approaches. Nanotechnology-based nano-delivery systems allow for new perspectives for atherosclerosis therapy. Surface-modified nanoparticles could achieve highly effective therapeutic effects by binding to specific receptors that are abnormally overexpressed in atherosclerosis, with less adverse effects on non-target tissues. The main purpose of this review is to summarize the research progress and design ideas to target atherosclerosis using a variety of ligand-modified nanoparticle systems, discuss the shortcomings of current vector design, and look at future development directions. We hope that this review will provide novel research strategies for the design and development of nanotherapeutics targeting atherosclerosis.

Camptothesome elicits immunogenic cell death to boost colorectal cancer immune checkpoint blockade.

Camptothesome is an innovative nanovesicle therapeutic comprising the sphingomyelin-derived camptothecin (CPT) lipid bilayer. In this work, we deciphered that Camptothesome was taken up by colorectal cancer (CRC) cells through primarily the clathrin-mediated endocytotic pathway and displayed the potential of eliciting robust immunogenic cancer cell death (ICD) via upregulating calreticulin, high mobility group box 1 protein (HMGB-1), and adenosine triphosphate (ATP), three hallmarks involved in the induction of ICD. In addition, use of dying MC38 tumor cells treated with Camptothesome as vaccine prevented tumor growth in 60% mice that received subsequent injection of live MC38 cells on the contralateral flank, validating Camptothesome was a legitimate ICD inducer in vivo. Camptothesome markedly reduced the acute bone marrow toxicity and gastrointestinal mucositis associated with free CPT and beat free CPT and Onivyde on anti-CRC efficacy and immune responses in a partially interferon gamma (IFN-γ)-dependent manner. Furthermore, Camptothesome enhanced the efficacy of immune checkpoint inhibitors to shrink late-stage orthotopic MC38 CRC tumors with diminished tumor metastasis and markedly prolonged mice survival.

Water quality assessment using optimized CWQII in Taihu Lake.

To improve the rationality of weight allocation and weight proportion of different periods in the process of water quality assessment, the comprehensive water quality identification index (CWQII) model was optimized in this study. A new improved comprehensive water quality identification index (ICWQIIG) model based on game theory was established to combine subjective weight and objective weight. Based on ICWQIIG, an improved comprehensive water quality identification index (ICWQIIP) model with phased period combination weights was established to determine determined the weight proportion of phased periods was established. In this study, CWQII, ICWQIIG, and ICWQIIP were used to evaluate the water quality of seventeen sites in Taihu Lake in 2020. The models selected nine water quality parameters and six water quality indicators. The assessment results of water quality classification were between "slightly polluted" and "moderately polluted". The pollution level on the east bank was lower than that on the west bank and north bank. Furthermore, it was also affected by seasonal change, water quality was worse in January and February but better in October and November. The mean value of Iwq calculated by CWQII, ICWQIIG, and ICWQIIP were 2.405, 2.833, and 3.000, respectively. The compared results showed that the ICWQIIG method can more representative identify the location of polluted water than CWQII. Moreover, the ICWQIIP method calculation results not only retained the representative polluted water samples in the ICWQIIG method but can also identify more pollution sites and worse polluted water bodies. Both ICWQIIG and ICWQIIP had high reliability and accuracy in assessment results, and ICWQIIP was more accurate under sufficient data conditions. This study can offer a scientific basis for local water resource management in Taihu Lake, while simultaneously proposing a science-based and valid methodology for the assessment of other similar water bodies.

Laser/GSH-Activatable Oxaliplatin/Phthalocyanine-Based Coordination Polymer Nanoparticles Combining Chemophotodynamic Therapy to Improve Cancer Immunotherapy.

There are two severe obstacles in cancer immunotherapy. The first is that the low response rate challenges the immune response owing to the immunosuppressive tumor microenvironment (ITM) and poor immunogenicity of the tumor. The second obstacle is that the dense and intricate pathophysiology barrier seriously restricts deep drug delivery in solid tumors. A laser/glutathione (GSH)-activatable nanosystem with tumor penetration for achieving highly efficient immunotherapy is reported. The core of the nanosystem was synthesized by coordinating zinc ions with GSH-activatable oxaliplatin (OXA) prodrugs and carboxylated phthalocyanine. Such an OXA/phthalocyanine-based coordination polymer nanoparticle (OPCPN) was wrapped by a phospholipid bilayer and NTKPEG. NTKPEG is a PEGylated indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor prodrug containing a thioketal (TK) linker, which was modified on the OPCPN (OPCPN@NTKPEG). Upon the laser irradiation tumor site, ROS production of the OPCPN@NTKPEG triggers cleavage of NTKPEG by degradation of TK for promoted tumor penetration and uptake. OXA, phthalocyanine, and IDO1 inhibitor were released by the intracellular high-level GSH. OXA inhibits cell growth and is combined with photodynamic therapy (PDT) to induce immunogenic cell death (ICD). The IDO1 inhibitor reversed the ITM by suppressing IDO1-mediated Trp degradation and exhaustion of cytotoxic T cells. Laser/GSH-activatable drug delivery was more conducive to enhancing ICD and reversing ITM in deep tumors. Chemo-PDT with OPCPN@NTKPEG significantly regressed tumor growth and reduced metastasis by improved cancer immunotherapy.

Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges.

Even though nanoparticle drug delivery systems (nanoDDSs) have improved antitumor efficacy by delivering more drugs to tumor sites compared to free and unencapsulated therapeutics, achieving satisfactory distribution and penetration of nanoDDSs inside solid tumors, especially in stromal fibrous tumors, remains challenging. As one of the most common stromal cells in solid tumors, tumor-associated fibroblasts (TAFs) not only promote tumor growth and metastasis but also reduce the drug delivery efficiency of nanoparticles through the tumor's inherent physical and physiological barriers. Thus, TAFs have been emerging as attractive targets, and TAF-targeting nanotherapeutics have been extensively explored to enhance the tumor delivery efficiency and efficacy of various anticancer agents. The purpose of this Review is to opportunely summarize the underlying mechanisms of TAFs on obstructing nanoparticle-mediated drug delivery into tumors and discuss the current advances of a plethora of nanotherapeutic approaches for effectively targeting TAFs.

Enhancing TNBC Chemo-immunotherapy via combination reprogramming tumor immune microenvironment with Immunogenic Cell Death.

Tumor-associated fibroblasts (TAFs) play an important role in tumor progression and therapeutic response, especially in the immunosuppressive tumor microenvironment (TME). To remodel immunosuppressive TME of 4T1 tumor, we developed a nano liposome to deliver silybin (SLN, an anti-liver fibrosis Chinese Traditional Medicine). Liposomal silybin (SLN/LIP) possessed a spherical shape with particle sizes of 75.2 nm, high stability, and good accumulation in the tumor site. After treated with SLN/LIP, α-SMA positive TAFs and the deposition of stroma were decreased significantly. SLN/LIP also changed the tumor immune microenvironment through the increase of IFN-γ and IL-12, as well as reduced of TGF-ß, SDF-1, IL6 and TNF-α. Importantly, SLN/LIP enhanced the infiltration of cytotoxic T cells (CTLs) and transformed a "cold" tumor into a "hot" tumor. To achieve the higher antitumor efficacy, an immunogenic cell death (ICD) inducer, liposomal doxorubicin (DOX/LIP) was combined with SLN/LIP. The combination treatment led to trigger immunogenic tumor apoptosis, and enhance antitumor immunity, therefore, improved anti-tumor efficiency, and further prolonged survival duration. The combination of liposomal silybin and liposomal doxorubicin might be a new chemo-immunotherapy approach for triple negative breast cancer (TNBC) tumor treatment.

Folate Modified Long Circulating Nano-Emulsion as a Promising Approach for Improving the Efficiency of Chemotherapy Drugs in Cancer Treatment.

PURPOSE: In order to improve the therapeutic efficiency of the chemotherapeutic drug paclitaxel in tumors, a folate-based Paclitaxel nanoemulsion (FNEs) was developed for tumor targeted treatment. METHODS: In this study, we designed a folate-targeted nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) based on the traditional nanoemulsion using the principle of long-circulation targeting receptor mediated. The nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) was fabricated using high-pressure homogenization with a microfluidizer. RESULTS: The nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) can improve the delivery efficiency of nanocarriers at the tumor site by virtue of the high expression of folate receptors on the tumor surface. Malvern Nanoseries device and transmission electron microscopy (TEM) analyses showed that the nanoemulsions were spherical with an average diameter of 140 nm. The nanoemulsions can effectively carry paclitaxel (PTX) with an encapsulation rate of about 95%. And in vitro experiments have shown that it can efficiently increase the uptake of PTX in 4 T1 breast cancer cells and FNEs had a targeting capability hundredfold higher than that of PTX-loaded nanoemulsions (PTX-NEs) without folate. In vivo experiments have shown that the pharmacokinetic parameters of FNEs were better than those of other PTX groups and FNEs can significantly enhance circulation time in the body of the subcutaneously implanted 4 T1 breast cancer in mice, increase the accumulation of chemotherapy drugs at tumor sites and effectively inhibit tumor growth with lower system toxicity. CONCLUSIONS: This study can effectively improve the therapeutic efficiency of chemotherapy drugs for tumors, and provide an useful reference for solving the problem of low efficacy of chemotherapy drugs in clinical treatment of tumors. Graphical Abstract Schematic representation of Folic acid/PEG-DSPE/nano-emulsion (FNEs) specifically target tumor cells and enhanced anti-tumor effects.