Identification of exosomal miR-484 role in reprogramming mitochondrial metabolism in pancreatic cancer through Wnt/MAPK axis control.

The microRNAs (miRNAs) are potent regulators of tumorigenesis in various cancers, especially pancreatic cancer. The abnormal expression of miRNAs can be observed in tumor cells. Noteworthy, miRNAs could be transferred by exosomes as small extracellular vesicles in regulation of carcinogenesis. This research focused on exploring the roles and mechanisms of exosomal miR-484, derived from human bone marrow mesenchymal stem cells (hBMSCs), in the context of molecular interactions and regulation of mitochondrial metabolism. Exosomes were isolated for the examination of miR-484 expression. The impacts of hBMSCs-derived exosomal miR-484 on pancreatic cancer cells were studied using various assays. Evaluation of mitochondrial function and metabolism was performed. Wnt/MAPK pathway-related protein expression was assessed, and an in vivo tumor xenograft model was utilized to examine the functions. Our findings demonstrated a decreased miR-484 expression in pancreatic cancer cells. However, hBMSCs-derived exosomal miR-484 inhibited the proliferation and migration of these cells, while inducing apoptosis. Moreover, miR-484 led to an upsurge in reactive oxygen species production, a decrease in ATP levels, and a disruption in mitochondrial metabolism. In vivo analyses showed that hBMSCs-derived exosomal miR-484 lessened tumor size and weight, while also suppressing the expression of mitochondrial biomarkers. Further, there was a decline in ß-catenin and p-p38 protein levels both in vitro and in vivo. The addition of LiCl restored the disrupted mitochondrial metabolism. Conclusively, our results suggest that hBMSCs-derived exosomal miR-484 mitigates the malignant transformation and mitochondrial metabolism of pancreatic cancer by deactivating the Wnt/MAPK pathway.

Efficacy of laparoscopic repeat hepatectomy compared with open repeat hepatectomy: a single-center, propensity score matching study.

INTRODUCTION: Laparoscopic repeat hepatectomy (LRH) is considered to be a technically challenging procedure which has not been widely applied. This study aimed to assess the accessibility and security of LRH for patients with hepatic tumor recurrence. METHODS: Between January 2010 and October 2020, we performed 48 LRHs and 31 open repeat hepatectomies (ORHs) for recurrent liver cancer. LRHs were matched to ORHs (1:1) using propensity score matching (PSM) created by comparing preoperative factors. The perioperative data of patients were retrospectively analyzed, including baseline data, operative time, intraoperative blood loss, pathology, days of postoperative stay, complication morbidity, and mortality within 30 days. Overall survival and recurrence-free survival rates with appropriate follow-up were obtained to evaluate the long-term outcomes. RESULTS: Compared with the ORH, LRH was related with shorter operative duration (169.9 versus 232.9 ml, p < 0.01), less intraoperative bleeding (100.0 versus 500.0 ml, p < 0.01), lower rate of blood transfusion (8.3% versus 58.1%, p < 0.01), and shorter hospitalization (5.0 versus 11.0 days, p < 0.01). The median follow-up was 31 months. The LRH 1-, 3-, and 5-year overall survival were 77.1%, 61.6%, and 46.2% versus 82.3%, 66.5%, and 29.5% for ORH (p = 0.77). The 1-, 3-, and 5-year disease-free survival rates of the two groups were 73.4%, 62.0%, and 44.3% versus 66.1%, 44.1%, and 14.7%, respectively (p = 0.22). CONCLUSIONS: Laparoscopic repeated hepatectomy is safe and practicable with great short-term results for selected patients.

Safety and feasibility of laparoscopic liver resection for hepatocellular carcinoma with clinically significant portal hypertension: a propensity score-matched study.

BACKGROUND: The presence of clinically significant portal hypertension (CSPH) remains a relative contraindication to liver resection for patients with resectable hepatocellular carcinoma (HCC). The goal of this study was to explore whether a laparoscopic approach could extend the indications for hepatectomy to patients with PH. METHOD: Patients who underwent laparoscopic liver resection (LLR) from February 2016 to September 2019 performed by a single medical team were included in this study. We analyzed the surgical and oncological outcomes between groups with and without CSPH before and after propensity score matching (PSM). RESULT: We enrolled 156 patients divided into two groups according to the presence (CSPH, n = 26) or absence (non-CSPH, n = 130) of CSPH. CSPH group was associated with more clinical signs of liver dysfunction (p < 0.05). After PSM (n = 48 patients), the CSPH group tended to have a longer postoperative hospital stay (p = 0.054); however, there was no difference in operation time (p = 0.329), blood loss volume (p = 0.392), transfusion rates (p = 0.701), rate of conversion to open surgery (p = 0.666), surgical margin (p = 0.306), surgical mortality (n = 0), or comprehensive complication index (p = 0.844) between the two groups. The median follow-up time for the entire cohort was 19.6 months (range 0.2-40.6 months). The 3-year overall survival rate was 62.9% in the CSPH group and 84.3% in the non-CSPH group (p = 0.1090), and results were similar after PSM (p = 0.5734). CONCLUSIONS: LLR is safe and feasible for HCC with PH. The introduction of minimally invasive surgery, represented by LLR, can appropriately expand the indications for hepatectomy.

Safety and effectiveness evaluation of a two-handed technique combining harmonic scalpel and laparoscopic Peng's multifunction operative dissector in laparoscopic hemihepatectomy.

OBJECTIVES: This study was designed to evaluate the safety and effectiveness of a two-hand technique combining harmonic scalpel (HS) and laparoscopic Peng's multifunction operative dissector (LPMOD) in patients who underwent laparoscopic hemihepatectomy (LHH). METHODS: We designed and conducted a case-control study nested in a prospectively collected laparoscopic liver surgery database. Patients who underwent LHH for liver parenchyma transection using HS + LPMOD were defined as cases (n = 98) and LPMOD only as controls (n = 47) from January 2016 to May 2018. Propensity score matching (1:1) between the case and control groups was used in the analyses. RESULTS: The case group had significantly less intraoperative blood loss in milliliters (169.4 ± 133.5 vs. 221.5 ± 176.3, P = 0.03) and shorter operative time in minutes (210.5 ± 56.1 vs. 265.7 ± 67.1, P = 0.02) comparing to the control group. The conversion to laparotomy, postoperative hospital stay, resection margin, the mean peak level of postoperative liver function parameters, bile leakage rate, and others were comparable between the two groups. There was no perioperative mortality. CONCLUSIONS: We demonstrated that the two-handed technique combing HS and LPMOD in LHH is safe and effective which is associated with shorter operative time and less intraoperative blood loss compared with LPMOD alone. The technique facilitates laparoscopic liver resection and is recommended for use.

Differentiation and management of hepatobiliary mucinous cystic neoplasms: a single centre experience for 8 years.

BACKGROUND: Hepatobiliary mucinous cystic neoplasms (H-MCNs) are relatively rare cystic neoplasms in the liver. The differential diagnosis of H-MCNs remains big challenging, and the management and prognosis between the hepatic simple cyst (HSC) and H-MCNs are quite different. This study aimed to present our experience in the management of H-MCNs and provide a preoperative H-MCNs risk prediction nomogram to differentiating H-MCNs from liver cystic lesions. METHODS: 29 patients diagnosed with H-MCNs and 75 patients diagnosed with HSC between June 2011 and June 2019 at Zhejiang University School of medicine, Sir Run-Run Shaw Hospital were reviewed in this study. We analyzed the demographic and clinicopathological variables. RESULTS: US, CT, and MRI could accurately diagnose only 3.4%, 46.1%, and 57.1% of H-MCNs, respectively. After univariate analysis and multivariate logistic regression analysis, the variables significantly associated with H-MCNs were enhancement after contrast (p = 0.009), tumour located in the left lobe (p = 0.02) and biliary ductal dilation (p = 0.027). An H-MCNs risk predictive nomogram was constructed, which showed excellent discrimination (areas under the receiver operating characteristic curve were 0.940) and consistent calibration between the predicted probability and actual probability. CONCLUSION: Among patients with H-MCNs, the location of the tumour, enhancement in CT scan, and biliary duct dilation are significantly independent risk factors. The appropriate treatment of H-MCNs is radical resection. Using our Nomogram could facilitate screening and identification of patients with liver cystic lesions.

Laparoscopic anatomical portal territory hepatectomy using Glissonean pedicle approach (Takasaki approach) with indocyanine green fluorescence negative staining: how I do it.

BACKGROUND: Laparoscopic anatomical resection (LAR) is a highly challenging procedure. This study aimed to describe our experience of the LAR with an indocyanine green fluorescence negative staining (ICGNS) by the Glissonean pedicle transection (Takasaki) approach. METHODS: From April 2017 to December 2019, 43 consecutive patients underwent LAR with ICGNS strategy in our medical team. The details of the ICGNS strategy were described. The demographic and clinicopathological data of the included patients were retrospectively analyzed. RESULTS: The extent of resections included right hemihepatectomy (n = 12), left hemihepatectom (n = 4), left lateral sectionectomy (n = 3), Right anterior sectionectomy (n = 3), Right posterior sectionectomy (n = 6), central hepatectomy (n = 2), single anterolateral segmentectomy (n = 5), single posterosuperior segmentectomy (n = 6), and bisegmentectomy (n = 2). The mean operation time was 212 ± 53 min, and the median estimated blood loss was 200 (100-300) ml. The overall complication rate was 30.2% (grade I, 14%; grade II, 14%; grade III, 2.3%). The median duration of postoperative hospital stay was 6 (4-7) days. CONCLUSION: ICGNS is a safe and feasible LAR strategy that greatly facilitates selecting the liver transection plane, although its benefits need to be verified by large-sample comparative studies.

A retrospective pilot study to examine the feasibility of real-time navigation for laparoscopic liver resections in intrahepatic cholangiocarcinoma using fusion indocyanine green fluorescence imaging.

BACKGROUND AND OBJECTIVES: Recently, PINPOINT, a novel laparoscopic fusion indocyanine green fluorescence imaging (IGFI) system has become available for laparoscopic liver resection. This study aims to characterize fluorescence patterns of intrahepatic cholangiocarcinoma (ICC) using the negative counterstaining method in laparoscopic anatomical hepatectomies of ICC. METHODS: Eleven consecutive patients, diagnosed with intrahepatic cholangiocarcinoma and underwent laparoscopic liver resection between April 2017 and December 2018, were retrospectively reviewed. A laparoscopic IGFI navigation system was used to characterize fluorescence patterns of ICC with intraoperative liver segment demarcation by means of negative counterstaining. RESULTS: Fusion IGFI of ICC was successfully obtained from all 11 patients from the surgical specimens. The fluorescence patterns of ICC can be categorized into rim-type fluorescence and segmental fluorescence, depending on tumor growth. In eight patients, indocyanine green fluorescence imaging was used to identify the hepatic lobes or segments by negative counterstaining. In six cases, a valid and persistent demarcation was achieved intraoperatively. CONCLUSION: Laparoscopic IGFI system could identify different types of ICC lesions and may facilitate real-time navigation for laparoscopic anatomic liver resection of ICC.

A novel simple intra-corporeal Pringle maneuver for laparoscopic hemihepatectomy: how we do it.

INTRODUCTION: To prevent and control hemorrhage is the key to successfully perform laparoscopic hemihepatectomy (LHH). Pringle's maneuver (PM) is the standard hepatic inflow occlusion technique. Our study was to describe a novel simple way to perform totally intra-corporeal laparoscopic PM and to explore the feasibility of combining PM and selective hemihepatic vascular occlusion technique in LHH. METHODS: We extracted and analyzed the data of patients who consecutively underwent LHH to validate this new surgery technique. Between January, 2016 and December, 2017, 34 patients were included. Data of pre-operation, operation and post-operation were collected, including some demographic data, operative time, operative blood loss, transfusion rate, hepatic hilum occlusion rate and time, pathologic results, short-term complication, and postoperative hospitalization days. RESULTS: Only one patient (3.0%) in our series required conversion to laparotomy as a result of the severe adhesion. The average operative time was 216.9 ± 60.3 min. The mean hepatic inflow occlusion time was 25.3 ± 14.5 min. The average estimated blood loss was 192.9 ± 152.2 ml. All patients received R0 resection. CONCLUSION: The novel hepatic inflow occlusion device is a safe reliable and convenient technique for LHH that is associated with favorable perioperative outcomes and low risk of conversion.

Enhanced recovery care versus traditional care after laparoscopic liver resections: a randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS), with several evidence-based elements, has been shown to shorten length of hospital stay and reduce perioperative hospital costs in many operations. This randomized clinical trial was performed to compare complications and hospital stay of laparoscopic liver resection between ERAS and traditional care. METHODS: A randomized controlled trial was performed for laparoscopic liver resection from August 2015 to August 2016. Patients were randomly divided into ERAS group and traditional care group. The primary outcome was length of hospital stay (LOS) after surgery. Second outcomes included postoperative complications, hospital cost, and 30-day readmissions. Elements used in ERAS group included more perioperative education, nurse navigators, nutrition support for liver diseases, respiratory therapy, oral carbohydrate 2 h before operation, early mobilization and oral intake, goal-directed fluid therapy, less drainages, postoperative nausea and vomiting (PONV) prophylaxis and multimodal analgesia. RESULTS: The study included 58 (two conversion to laparotomy) patients in ERAS group and 61 (three conversion to laparotomy) patients in the traditional care group. Postoperative LOS was significantly shorter in the ERAS group than traditional care group (5 vs. 8 days; p < 0.001). ERAS program significantly reduced the hospital costs (CNY 45413.1 vs. 55794.1; p = 0.006) and complications (36.2 vs. 55.7%; p = 0.033). Duration till first flatus and PONV were significantly reduced in ERAS group. Pain control was better in ERAS (Visual analogue scale (VAS) POD1 (≥ 4) 19.0 vs. 39.3%, p = 0.017; VAS POD1 2.5 vs. 3.1, p = 0.010). There was no difference in the rate of 30-day readmissions (6.9 vs. 8.2%; p = 1.000). CONCLUSION: ERAS protocol is feasible and safe for laparoscopic liver resection. Patients in ERAS group have less pain and complications.

The role of exosomes in hepatitis, liver cirrhosis and hepatocellular carcinoma.

Exosomes are small vesicles that were initially thought to be a mechanism for discarding unneeded membrane proteins from reticulocytes. Their mediation of intercellular communication appears to be associated with several biological functions. Current studies have shown that most mammalian cells undergo the process of exosome formation and utilize exosome-mediated cell communication. Exosomes contain various microRNAs, mRNAs and proteins. They have been reported to mediate multiple functions, such as antigen presentation, immune escape and tumour progression. This concise review highlights the findings regarding the roles of exosomes in liver diseases, particularly hepatitis B, hepatitis C, liver cirrhosis and hepatocellular carcinoma. However, further elucidation of the contributions of exosomes to intercellular information transmission is needed. The potential medical applications of exosomes in liver diseases seem practical and will depend on the ingenuity of future investigators and their insights into exosome-mediated biological processes.

The ALPPS in the Treatment of Hepatitis B-Related Hepatocellular Carcinoma With Cirrhosis: A Single-Center Study and Literature Review.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been reported to be a new treatment strategy for patients with predicted small volumes of future liver remnant (FLR). ALPPS is associated with rapid hypertrophy of FLR but it has a high postoperative mortality and morbidity. Up to now, it is controversial to apply ALPPS in hepatocellular carcinoma, especially for patients with liver cirrhosis. METHODS: Between May 2014 and June 2015, consecutive patients who underwent ALPPS with hepatitis B-related hepatocellular carcinoma with cirrhosis carried out in our center were included into the study. Demographic characteristics, surgical outcomes, and pathological results were evaluated. Subsequently, follow-up was still in progress. RESULTS: The median operating time of the first (n = 12) and the second procedures (n = 10) were 285.0 and 212.5 minutes, respectively. The median blood loss were 200 and 800 mL for 2 stages of operations. The severe complication (≥IIIB) rates for the first and the second operations were 25.0% versus 40.0%, respectively. Six patients with too small future live remnant died of postoperative hepatic failure. On a median follow-up of 16 months of the 6 patients discharged, 4 patients were still alive and of 2 were disease-free. CONCLUSION: In terms of the feasibility and safety, this study showed that ALPPS in the treatment of hepatocellular carcinoma with insufficient future liver remnant might be a double-edged sword, and careful patients selected was proposed. Too small of FLR/SLV, less than 30%, is not recommended for ALPPS in liver with cirrhosis.

A Strong Adhesive Biological Hydrogel for Colon Leakage Repair and Abdominal Adhesion Prevention.

Colon leakage is one of the most severe complications in abdominal trauma or surgery cases. It can lead to severe abdominal infection and abdominal adhesions, resulting in prolonged hospital stays and increased mortality. In this study, a photosensitive hydrogel is proposed, which can swiftly form a strong adhesion coating on the damaged colon after UV irradiation, to realize quick cure and suture-free repair of colon leakage. The newly developed biological gel consists of hyaluronic acid methacryloyl (HAMA) and hyaluronic acid o-nitroso benzaldehyde (HANB) in the optimal ratio of 3: 1, which exerts both the rapid photocuring properties of HAMA and the strong tissue adhesion properties of HANB. HAMA/HANB shows excellent adhesion stability on wet surfaces, presenting controllable mechanical properties, ductility, adhesion stability, and chemical stability; it also evades foreign body response, which relieves the degree of abdominal adhesion. The underlying mechanism for HAMA/HANB promoting wound healing in colon leakage involves the reconstruction of the colon barrier, as well as the regulation of the immune reaction and neovascularization. In all, HAMA/HANB is a promising alternative suture-free approach for repairing colon leakage; it has a reliable healing effect and is expected to be extended to clinical application for other organ injuries.

Global Trends in Research of Antimicrobial Peptides for the Treatment of Drug-Resistant Bacteria from 1995 to 2021: A Bibliometric Analysis.

Background: Antimicrobial peptides (AMPs) can act on the bacterial cell membrane to play an antibacterial role in types of drug-resistant bacteria. Therefore, AMPs have attracted more and more attention in the treatment of drug-resistant bacteria. Methods: Bibliometric analysis was employed to sort out the development and trends in the research of AMPs in the treatment of drug-resistant bacteria and map the knowledge structure for scholars. Results: Since 2010, the publications and citations in this field have exploded, indicating a growing global interest in the field of AMPs for the treatment of drug-resistant bacteria. And as major countries in this field, China and the USA had conducted very in-depth exchanges and cooperation, which had injected a steady stream of impetus into this field. Both old and new scholars have made efforts, and related fields have developed rapidly, especially in the synthesis and improvement of novel AMPs. In recent years, research directions in the field of AMPs for the treatment of drug-resistant bacteria gradually focused on the practical application, optimization of drug delivery mode, optimization of synthesis mode, screening of new AMPs and other fields, indicating that the relevant research results of AMPs for the treatment of drug-resistant bacteria had entered the actual clinical stage, with higher practical significance. Conclusion: The research history, global research status, future research hotspots, and trends of the research of AMPs in the treatment of drug-resistant bacteria were discussed in depth in this study, which can provide research references and inspiration for researchers inside and outside the related field.

Microbiota Regulates Pancreatic Cancer Carcinogenesis through Altered Immune Response.

The microbiota is present in many parts of the human body and plays essential roles. The most typical case is the occurrence and development of cancer. Pancreatic cancer (PC), one of the most aggressive and lethal types of cancer, has recently attracted the attention of researchers. Recent research has revealed that the microbiota regulates PC carcinogenesis via an altered immune response. Specifically, the microbiota, in several sites, including the oral cavity, gastrointestinal tract, and pancreatic tissue, along with the numerous small molecules and metabolites it produces, influences cancer progression and treatment by activating oncogenic signaling, enhancing oncogenic metabolic pathways, altering cancer cell proliferation, and triggering chronic inflammation that suppresses tumor immunity. Diagnostics and treatments based on or in combination with the microbiota offer novel insights to improve efficiency compared with existing therapies.

GelNB molecular coating as a biophysical barrier to isolate intestinal irritating metabolites and regulate intestinal microbial homeostasis in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier. Due to the poor remission effect and severe adverse events associated with current clinical medications, IBD remains an incurable disease. Here, we demonstrated a novel treatment strategy with high safety and effective inflammation remission via tissue-adhesive molecular coating. The molecular coating is composed of o-nitrobenzaldehyde (NB)-modified Gelatin (GelNB), which can strongly bond with -NH2 on the intestinal surface of tissue to form a thin biophysical barrier. We found that this molecular coating was able to stay on the surface of the intestine for long periods of time, effectively protecting the damaged intestinal epithelium from irritations of external intestinal metabolites and harmful flora. In addition, our results showed that this coating not only provided a beneficial environment for cell migration and proliferation to promote intestinal repair and regeneration, but also achieved a better outcome of IBD by reducing intestinal inflammation. Moreover, the in vivo experiments showed that the GelNB was better than the classic clinical medication-mesalazine. Therefore, our molecular coating showed potential as a promising strategy for the prevention and treatment of IBD.

Isolated biliary cryptococcosis manifesting as obstructive jaundice in an immunocompetent adult.

Cryptococcosis is a symptomatic fungal infection caused by Cryptococcus, which frequently occurs in patients who are immunologically compromised or chronically ill. Localized involvement of the hepatobiliary system in an immunocompetent adult is extremely rare. We report a unique case of isolated biliary cryptococcosis manifesting as obstructive jaundice and mimicking hilar cholangiocarcinoma in an immunocompetent woman. By integrating surgical and antifungal drug therapy, the disease was effectively controlled. Despite an increasing incidence of biliary malignancies, hepatobiliary surgeons and gastroenterologists must maintain a high index of suspicion for other rare possibilities of non-specific biliary inflammation.

Radiomics Analysis of Gd-EOB-DTPA Enhanced Hepatic MRI for Assessment of Functional Liver Reserve.

Rationale and Objectives To evaluate the effectiveness of radiomics analysis based on Gd-EOB-DTPA enhanced hepatic MRI for functional liver reserve assessment in HCC patients. Materials and Methods Radiomics features were extracted from Gd-EOB-DTPA enhanced MRI images in 60 HCC patients. Boruta algorithm was performed to select features associated with indocyanine green retention rate at 15 min (ICG R15). Prediction and classification model were built by performing Random Forest regression analysis. Pearson correlation analysis and AUC of ROC were used to assess performance of the two models. Results A total of 165 radiomics features were extracted. Six radiomics features were selected to build the prediction model. A Predicted value of ICG R15 for each patient was calculated by the prediction model. Pearson correlation analysis revealed that predicted values were significantly associated with actual values of ICG R15 (R value = 0.90, p < 0.001). Nine radiomics features were selected to build the classification model. AUC of ROC revealed favorable performance of the classification model for identifying patients with ICG R15 <10% (AUC: 0.906, 95%CI: 0.900-0.913), <15% (AUC: 0.954, 95%CI: 0.950-0.958), and <20% (AUC: 0.996, 95%CI: 0.995-0.996). Conclusion Radiomics analysis of Gd-EOB-DTPA enhanced hepatic MRI can be used for assessment of functional liver reserve in HCC patients.

Synthesis of Strong Adhesive Hydrogel, Gelatin O-Nitrosobenzaldehyde.

Adhesive materials have become popular biomaterials in the field of biomedical and tissue engineering. In our previous work, we presented a new material - gelatin o-nitrosobenzaldehyde (gelatin-NB) - which is mainly used for tissue regeneration and has been validated in animal models of corneal injury and inflammatory bowel disease. This is a novel hydrogel formed by modifying biological gelatin with o-nitrosobenzaldehyde (NB). Gelatin-NB was synthesized by activating the carboxyl group of NB-COOH and reacting with gelatin through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The obtained compound was purified to generate the final product, which can be stably stored for at least 18 months. NB has a strong adhesion to -NH2 on the tissue, which can form many C = N bonds, thus increasing the adhesion of gelatin-NB to the tissue interface. The preparation process comprises steps for the synthesis of the NB-COOH group, modification of the group, synthesis of gelatin-NB, and purification of the compound. The goal is to describe the specific synthesis process of gelatin-NB in detail and to demonstrate the application of gelatin-NB to damage repair. Moreover, the protocol is presented to further strengthen and expand the nature of the material produced by the scientific community for more applicable scenarios.

Platelet-Vesicles-Encapsulated RSL-3 Enable Anti-Angiogenesis and Induce Ferroptosis to Inhibit Pancreatic Cancer Progress.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers. It is characterized by stromal richness, lack of blood supply and special metabolic reprogramming in the tumor microenvironment, which is difficult to treat and easy to metastase. Great efforts have been made to develop new drugs which can pass through the stroma and are more effective than traditional chemotherapeutics, such as ferroptosis inducers-Erastin and RSL-3. As current anti-angiogenic therapy drugs alone are suboptimal for PDAC, novel vascular disruption agents in combination with ferroptosis inducers might provide a possible solution. Here, we designed human platelet vesicles (PVs) to camouflage RSL-3 to enhance drug uptake rate by tumor cells and circulation time in vivo, deteriorating the tumor vessels and resulting in tumor embolism to cut the nutrient supply as well as causing cell death due to excessive lipid peroxidation. The RSL-3@PVs can also cause the classic ferroptosis-related change of mitochondrial morphology, with changes in cellular redox levels. Besides that, RSL-3@PVs has been proved to have great biological safety profile in vitro and in vivo. This study demonstrates the promising potential of integrating PVs and RSL-3 as a combination therapy for improving the outcome of PDAC.