Kesum (Persicaria minus Huds.) is renowned in Asia for its biological activities, including those of its essential oil (KEO). Despite this, studies on the antibacterial properties and mechanisms of KEO are limited. This research investigates the antibacterial activity of KEO and its mechanisms of action against Staphylococcus aureus ATCC 29213 and Salmonella enterica ATCC 13076. KEO was extracted via hydro-distillation, and its constituents were identified using gas chromatography-mass spectrometry. An updated and thorough characterization of hydrodistilled KEO is presented in this review with a focus on the chemical-biological connections. KEO in vitro antioxidant activity was evaluated by assaying its total phenolic content and its 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. The GC-MS profiling indicated that aldehydes (decanal, dodecanal and tridecanal), terpenoids (β-caryophyllene, α-humulene and drimenin) and long-chain alcohol compounds with a membrane-active antibacterial properties and the ability to scavenge free radicals that dominate the KEO. KEO antibacterial activity was evaluated, alongside assays for cellular leakage, Fourier-Transform InfraRed spectroscopy (FTIR) and Atomic Force Microscopy (AFM). KEO demonstrated significant antibacterial activity against S. aureus ATCC 29,213, with a minimum inhibitory concentration (MIC) of 12.5 mg/mL and an inhibition zone diameter of 10.00 ± 1.2 mm. Consequently, the KEO showed notable antibacterial activity which against S. aureus and a considerable antioxidant capacity (DPPH: 82.35
Sodium alginate (SA) hydrogels have attracted considerable attention due to their excellent biocompatibility and protective effects on bioactive ingredients. However, single-polysaccharide network has insufficient mechanical strength, poor release control, and low efficiency in co-loading of hydrophilic/hydrophobic actives. In this study, beta-lactoglobulin nanofibrils (BLGF) with long fibril (LF) or worm-like fibril (WF) morphology were incorporated into the SA network via Ca2+ crosslinking. The resulting composite hydrogels significantly enhanced water-holding capacity and swelling properties reaching maximum values of 98.52% and 46.84%, respectively. While WF showed a higher binding interaction force with SA, LF demonstrated a more efficient intertwining effect, maintaining a dense gel network. Introducing solid lipid nanoparticles (SLN) resulted in an encapsulation efficiency of 88.19% for beta-carotene and a loading rate of 81.57% for folic acid. The composite hydrogel exhibited pH-responsive release reflected by the low release (<5%) of beta-carotene in the gastric phase and accelerated release in intestinal fluid. The hydrogel also exhibited a diffusion-controlled release pattern for folic acid and an erosion-controlled release pattern for beta-carotene. By varying the SA-LF/WF ratio, coordinated control over the diffusion rates of bioactives was achieved. This study clarifies the structural enhancement provided by BLGF in composite hydrogels and offers insights for designing dual-delivery systems.
Flaxseed dehulling generates substantial waste rich in valuable phytonutrients. This study developed a sustainable subcritical biphasic solvent extraction (SBE) using n-butane/ethanol to simultaneously recover lignans and oil from this byproduct. Optimization via Box-Behnken design achieved a total phenolic content (TPC) of 22.76 mg GAE/g DW under optimal conditions (69 degrees C, 2 h, and 200 mL ethanol). The predominant phenolic was identified as secoisolariciresinol diglucoside (SDG), which demonstrated significant antioxidant activity compared to ascorbic acid. Furthermore, Hansen solubility parameters modeling theoretically validated the high dissolution efficiency of the solvent system for SDG. The co-extracted oil exhibited a quality comparable to commercial flaxseed oil. Importantly, the SBE process showed negligible interference on the subsequent polysaccharide extraction, yielding 18.19 g/100 g compared to conventional hot water extraction (18.73 g/100 g) from raw dehulling waste. This work establishes SBE as an efficient and integrated strategy for the comprehensive valorization of flaxseed processing waste, maximizing resource utilization and economic value.
Diacylglycerol (DAG)-enriched margarines offer significant health advantages over traditional triacylglycerol (TAG) counterparts but require precise crystallization control to achieve desired textures. This study systematically quantified how chilling temperature (-10 degrees C to 10 degrees C) modulates the crystallization network, rheology, and functional performance of palm oil (PO)-DAG margarines (70:30 w/w). Results revealed that lower temperatures (-10 degrees C) enhanced nucleation rates, yielding denser crystalline scaffolds dominated by beta-polymorphs (52.11%), higher solid fat content, and an elevated storage modulus (G ' > 10(5) Pa). Conversely, higher temperatures (10 degrees C) promoted beta'-polymorphs (77.09%), smaller crystal sizes, and reduced hydrogen bonding. These crystallization characteristics collectively indicate that 0 degrees C is the optimal chilling temperature, as it increases beta'-polymorphic content and promotes the formation of fine needle-like crystals (D-f > 1.90) within a uniform network structure. Functionally, samples quenched at 0 degrees C achieved superior whipping performance, reducing specific gravity compared to 10 degrees C counterparts due to improved air incorporation while concurrently, maintaining competitive storage stability. This study establishes chilling temperature as a critical lever for tailoring health-oriented margarines providing the food industry with a scientific basis and precise processing parameter to manufacture next-generation margarines that deliver enhanced health benefits, superior texture, and improved functionality.
Fibrous (PPIA-2) and spherical (PPIA-8) pea protein isolate aggregates were prepared under controlled pH and heating conditions, and their influence on coconut diacylglycerol (CO-DAG)-based whipping cream were systematically evaluated. Compared with conventional triacylglycerol CO phases, CO-DAG reduced the interfacial energy barrier, promoted interfacial crystallization, and was favorable for protein adsorption. Fibrous aggregates exhibited enhanced interfacial activity and strong intermolecular entanglement ability, which facilitated bridging between fat globules and promoted partial coalescence. The synergistic effect between PPIA-2-12h and CO-DAG led to high overrun (200-250 %) and excellent foam stability. Spherical aggregates (PPIA-8) formed at 2 h exhibited weaker interfacial activity but could increase the rheological properties of foam by forming densely packed small fat globules. The combined influence of CO-DAG and protein aggregates with distinct morphologies defines the balance between foamability and stability. The study elucidated how aggregate morphology stabilizes foam by enhancing interfacial membranes and creating a three-dimensional network structure. These findings provide a theoretical and technical framework for designing plant-based low-fat whipping cream, emphasizing the dual role of DAG as a co-structuring lipid and protein aggregates as morphology-dependent stabilizers.
【Objective】Sweet cherry (Prunus avium L.) is highly valued for its bright coloration, crisp texture and pleasant sweetness; however, its high metabolic activity and fragile skin make the fruit extremely vulnerable to postharvest deterioration, particularly under cold storage, where weight loss, textural decline and color fading frequently occur. In recent years, melatonin (MT) has been reported to participate in plant stress mitigation and postharvest physiological regulation, yet the effects of preharvest application on cold-stored sweet cherries remain insufficiently defined, especially regarding cultivar-dependent responses. Therefore, this study aimed to evaluate the influence of different MT concentrations applied at various developmental stages on fruit physicochemical quality during refrigerated storage, and to provide theoretical guidance for the precise application of melatonin in sweet cherry production.【Methods】Two commercial sweet cherry cultivars, Luying 3 and Luying 5, grown under identical orchard conditions, were subjected to foliar sprays of exogenous MT at the hard-core stage(25 days after full bloom, DAFB), the color-break stage (45 DAFB) , and three days before harvest (55 DAFB) . Multiple MT concentrations were compared. After harvest, the fruits were stored at 4℃ under controlled relative humidity. At 0, 7 and 14 days of storage, weight loss, total soluble solids (TSS) content, texture profile analysis (TPA) parameters (including hardness, springiness, cohesiveness, gumminess and chewiness) , and color metrics (L*, a*, b*) were evaluated according to standard postharvest testing protocols. Multivariate analyses, including principal component analysis (PCA) and a correlation heatmap, were used to elucidate relationships among measured variables and to comprehensively discriminate the storage performance of different treatments. Statistical differences were tested at P≤0.05.【Results】The application of MT demonstrated clear concentration-and cultivar-dependent effects. During cold storage, weight loss increased significantly with storage time in both sweet cherry cultivars, with consistently higher values observed in Luying 5 than in Luying 3. High melatonin concentrations (0.30 mmol · L-1) significantly exacerbated weight loss at the late storage stage in both cultivars, whereas low to moderate concentrations partially alleviated weight loss at specific storage periods. Total soluble solids (TSS) content generally declined during storage; however, melatonin treatments differed in their ability to maintain TSS levels, with lower concentrations showing a relatively positive effect and higher concentrations accelerating TSS content depletion. In both cultivars, low-concentration MT (0.05-0.10 mmol · L-1) consistently preserved higher TSS content, implying a delayed reduction in fruit sweetness during cold storage. MT treatment also mitigated the decline of TPA hardness and maintained superior textural integrity, possibly by stabilizing cell wall structure or suppressing pectin solubilization. Colorimetric analyses revealed that MT inhibited undesirable increases in a* values and modulated shifts in L* and b*, implying delayed pigment oxidation and improved external appearance. Notably, fruit redness in MT-treated groups developed more uniformly, and surface brightness remained relatively stable. The correlation heatmap indicated that hardness, TSS content and chromatic parameters were positively associated and were critical determinants of fruit sensory acceptability. PCA analysis further demonstrated that these indicators accounted for the majority of variance among treatments, effectively distinguishing MT-treated fruits from the control at later storage stages. Cultivar-dependent responses were evident: Luying 5 exhibited high sensitivity to MT, particularly in adhesion-related texture attributes and mass retention, whereas Luying 3 displayed comparatively milder responsiveness across most parameters. At 14 days of storage, fruits treated with lower MT concentrations generally maintained higher overall quality scores, whereas excessive concentrations induced variable and sometimes negative results. These findings highlight the importance of dosage optimization in preharvest regulation.【Conclusion】Preharvest foliar application of melatonin at appropriate concentrations can effectively delay postharvest quality deterioration in sweet cherry fruits during cold storage. MT contributes to the maintenance of fruit weight, the conservation of soluble solid levels, the retention of desirable texture properties and the stabilization of color attributes. However, responses differ considerably among cultivars, underscoring the necessity of tailoring treatment strategies to specific genotypic characteristics. Low MT concentrations (0.05-0.10 mmol · L-1) are generally recommended for enhancing sweetness, firmness and surface brightness, while excessive concentrations may induce adverse effects, particularly in cultivars with lower tolerance.
Plant-based fat mimetics are increasingly needed as healthier and sustainable alternatives to animal fats. However, current emulsion gels are inherently limited in their capacity to replicate the thermal behavior of animal adipose tissue. In this study, pea protein fibril (PPF) and sodium alginate (SA) complexes were investigated for their potential to fabricate adipose tissue mimetics enhanced by glycerolized palm olein (PO). The PPF–SA complexes at mass ratios of 10:3 exhibited superior interfacial activity and a higher thermal degradation temperature compared to non-fibrillated complex. Cryo-scanning electron microscopy revealed that the PPF–SA complex coexisted around droplets forming an extracellular matrix-like network and providing thermal-responsive elasticity properties. Optimization of the oil/water ratio and Ca2+ concentration endowed the emulsion with a robust network architecture. The glycerolysis lipids provided thermal softening behavior, in which a higher monoacylglycerol (MAG) content effectively reduced interfacial tension and emulsion droplet size. The reduction consequently increased the available cross-linking sites within the PPF-SA network and significantly enhanced the oil binding capacity and freeze-thaw stability. This study demonstrates that PPF-SA in combination of glycerolysis lipids forms a cross-linking and crystalline network that simulates the thermo-responsive behavior to mimics that of porcine back fat.
ABSTRACT Natural phytochemicals derived from dietary sources have demonstrated promising anticancer potential with favorable safety profiles. Among them, Garcinone C (Gar. C), a xanthone derived from mangosteen (Garcinia mangostana), demonstrated superior antitumor activity compared to other derivatives in our preliminary screening. Here, we report the first comprehensive evaluation of the efficacy of Gar. C against triple‐negative breast cancer (TNBC) using both in vitro and in vivo models. Gar. C significantly inhibited cell viability and stemness in TNBC cell lines (SUM159 and SUM149) in a dose‐dependent manner, with IC50 values of 4.54 ± 0.13 µM and 5.97 ± 0.16 µM, respectively. Mechanistically, Gar. C induced mitochondrial‐mediated apoptosis, as indicated by an increased Bax/Bcl‐2 ratio and loss of mitochondrial membrane potential, and triggered G0/G1 cell cycle arrest via modulation of cyclin D1 and p21. Furthermore, Gar. C effectively suppressed cancer stemness, as evidenced by a reduced CD44+/CD24− population. RNA sequencing and Western blot analyses suggested that the inhibition of the Wnt/β‐catenin signaling pathway was a key mechanism contributing to its dual effects on inducing apoptosis and suppressing stemness. Importantly, in a xenograft mouse model using SUM159 cells, Gar. C significantly inhibited tumor growth and metastasis. These findings highlight the potential of Gar. C as a promising natural compound for the prevention and treatment of TNBC.
Flaxseed (Linum usitatissimum L.) has gained prominence in China, primarily attributed to its exceptional nutraceutical profile. However, defatted flaxseed meal is a major by-product that remains significantly underutilized, whose endogenous bioactive compounds (e.g., lignans, gum, cyclolinopeptide, and protein) deserve to be exploited for value-added utilization. The comprehensive utilization potential of flaxseed meals remains largely unexplored, thereby posing a critical challenge for sustainable agricultural development and circular economy implementation. Whereas prior reviews have predominantly examined individual flaxseed components regarding extraction, bioactivity, or applications, few have integrated these perspectives under a unified biorefinery framework to advance meal upcycling from waste to functional ingredients. Considering the zero-waste biorefinery concept, flaxseed meal could be upcycled into functional ingredients to accomplish Sustainable Development Goals. This review outlines the research progress on value-added processing of the main bioactive components in flaxseed meals to maximize their food and nutritional applications, including their basic properties, conventional and innovative extractions, and promising biological activities for further applications. Moreover, the challenges facing the comprehensive utilization of flaxseed meals were identified by considering food safety and consumer acceptability. In addition, suggestions for future industrial development are proposed to reduce food waste with additional revenue streams.
This study elucidates the covalent coordination mechanism underlying Zn2+ chelation by linusorbs (LOs) with different redox stages, highlighting the critical role of methionine (Met) residue. Fluorescence quenching, circular dichroism, and differential scanning calorimetry analyses demonstrated that Zn2+ interacts with LOs via a static quenching mechanism, forming stable complexes while reinforcing the secondary structural order and stability of LOs. The unoxidized LOs exhibit superior Zn2+-binding capacity (Ka = 20.3 L/mol), while oxidation to methionine sulfoxide/sulfone (MetO/MetO₂) significantly diminishes chelation efficacy. 1H NMR analysis identifies Zn2+-induced deshielding of the S-linked γ-CH₂ protons (Δδ = +0.03 ppm), with signal perturbations localized exclusively to the sulfur atom of Met, confirming exclusive coordination to the Met. Density functional theory and quantum topology analyses further validate the covalent characteristics of the S-Zn2+ bond (∇2ρ = -0.0696) and polarization of the S-(γ)CH2 bond triggered by sulfur's electron donation to Zn2+. LOs inhibit Zn2+-catalyzed lipid oxidation through specific covalent chelation.
Lipid nanoparticulate systems are efficient as active carriers with tailorable interfacial, crystallization profiles. In this study, medium-long chain diacylglycerol (MLCD)-based solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were constructed for curcumin (Cur) delivery to enhance its oral bioavailability and their Pickering stabilizing effects were evaluated. Cur-SLNs and NLCs stabilized by different surfactants, were prepared with particle sizes ranging from 148 to 305 nm. The nanoparticles were taken up by Caco-2 cells through clathrin and caveolae mediated endocytosis pathway, with the uptake efficiency of the NLCs being 2.25 - 3.94 fold higher than that of free Cur. The nanoparticles effectively inhibited the LPS-induced inflammatory response in RAW 264.7 cells, resulting in a 60 % reduction in NO secretion. Furthermore, these SLNs/ NLCs were utilized as Pickering stabilizers for water-in-oil (W/O) emulsions co-loaded with hydrophobic curcumin and hydrophilic NaCl. These emulsions demonstrated slow-release performance (78.23 - 96.12 % retention) after 4 weeks storage and exhibited tunable rheological properties. The interfacial particles effectively acted as a solid shell, impeding the release of internal phase compounds. The Ritger-Peppas model offered the best fit for the release profiles of all Cur-loaded lipid formulations. This study provides a theoretical basis and technical support for the fabrication and application of lipid nanoparticles and Pickering emulsions as a multifunctional delivery system.
Diacylglycerol (DAG) is a functional oil that can reduce body fat accumulation and postprandial triglycerides. In this study, lipase-catalyzed esterification of oleic acid with glycerol was investigated to elucidate the kinetics and selectivity of each reaction step. 1 H NMR monitoring revealed equilibrated positional isomerization among acylglycerols: sn-1 monoolein comprised 97.3 % of total monoacylglycerols, and sn-1,3 diolein comprised 73.3 % of total diacylglycerols. Acyl migration (isomer equilibration) occurred faster than overall esterification. The observed rate constants for successive esterification steps (glycerol -> monoacylglycerol, monoacylglycerol -> diacylglycerol, diacylglycerol -> triacylglycerol) were 0.01068, 0.00615, and 0.00304 min(-1) , respectively, indicating progressively slower reaction rates for larger acylglycerol species. Furthermore, molecular distillation at 200-220 degrees C purified the DAG without altering its fatty acid profile. These findings establish a kinetic model of the three-step esterification and highlight the importance of acyl migration in enzymatic DAG synthesis.
Ice cream is a popular frozen dessert highly favoured by consumers due to its creamy and smooth texture, light and airy properties, and rich taste contributed by dietary fats. However, its high calorie content poses several health risks. Nanofibrillated cellulose (NFC), composed of nanoscale fibres can replace fats in food by providing the necessary structural properties. This study produced NFC from palm dried long fibre (DLF), a by-product of the oil palm industry. The DLF-NFC exhibited high viscosity (108.23 ± 1.22 mPa s) and aspect ratio (27.61 ± 0.26) at a concentration of 0.6
Oral delivery of bioactive peptides by nanoparticles (NPs) plays an important role in drug administration for treating diseases. However, the delivery efficiency normally faces challenges such as gastrointestinal tract environment and barriers. Selecting the appropriate lipids and modulating the surface characteristics by polymers are critical to overcome the deficiencies. Herein, diacylglycerol (DAG) solid lipid nanoparticles (DAG-SLNs) modified with various surface agents were fabricated with glyceryl tristearate (TG) and cetyl palmitate (CP) as lipid controls. The results indicated that polydopamine (PDA) and polyethylene glycol (PEG) modifications reduced the hydrophobic interactions between nanoparticles and mucin, which subsequently enhanced penetration. Meanwhile, the low surface hydrophobicity of DAG particles resulted in higher mucus penetration ability than TG and CP SLNs. Caco-2/HT-29 uptake of particles primarily occurred via the lipid raft/caveolae-mediated pathway. The interaction between the quinone structure of PDA and the hydroxyl groups endowed the DAG particles with excellent transmembrane capability. The particles showed high delivery efficiency for flaxseed cyclopeptide with increased anti-inflammatory efficiency due to the high permeability in Caco-2/HT-29 and RAW 264.7 macrophages. This study provides insights into modulating the interaction of particles with cells in the mucosa and provides essential support for the rational design and application of lipid nanocarriers with high delivery efficiencies.
Tocotrienols (T3) are bioactive compounds with diverse biological activities, but their lipophilicity and poor bioavailability limit their application in the food field. In this study, surfactant-free self-assembled T3 nanoparticles (STNPs), β-lactoglobulin (BLG)-T3 co-assembled nanoparticles (BTNPs) and carboxymethyl chitosan (CMS)-T3 co-assembled nanoparticles (CTNPs) were comparatively evaluated. BTNPs exhibited higher encapsulation efficiency (EE, 82%–99%) and loading capacity (LC, 9–25 g/100g), along with smaller particle size (143–198 nm) than STNPs (179–236 nm). Spectroscopic investigations confirmed intermolecular interactions between T3 and carriers. Isothermal titration calorimetry revealed that BLG possessed significantly higher binding affinity toward T3 compared to CMS. Importantly, BTNPs exhibited better pH stability, salt tolerance and storage stability than STNPs and CTNPs. The bioaccessibility of T3 was largely enhanced in all nanoparticles systems. Furthermore, compared to STNPs, BTNPs and CTNPs exhibited stronger hydrophilic-radical scavenging capacities and superior protective effects against H2O2-induced oxidative stress in HepG2 cells.
In this study, we developed triptolide (TP)-loaded open-pore PBVHx microspheres (TP@OPMs) and compared their anticancer and embolization capabilities with those of TP-loaded sealed PBVHx microspheres (TP@SMs). TP@OPMs, characterized by an open surface and interconnected internal pores, showed higher water absorption (2860%) and porosity (79.69%), but slightly lower TP encapsulation efficiency (79 ± 0.32%) compared to TP@SMs, and achieved sustained TP release of 75.29% over 21 days. All PBVHx microspheres without TP demonstrated good biocompatibility, but TP@OPMs exhibited superior inhibitory effects on HepG2 cells compared to TP@SMs, with a hemolysis rate below 5%. In in vivo central arterial embolization experiments, TP@OPMs outperformed other microspheres and commercial gelatin microspheres, achieving the highest necrosis rate (50.70%). This resulted in the successful induction of ischemic necrosis and tissue detachment. These findings suggest that TP@OPMs are not only an effective drug delivery system but also have significant potential in embolization applications. This strategy provides a promising approach for the treatment of hepatocellular carcinoma and other malignant tumors.
Excessive animal fat intake drives interest in developing plant-based gels as sustainable and healthier fat substitutes. However, maintaining a rheology resemblance to animal fat while achieving clean-label and nutritional features remains challenging. This study explores the use of pea protein fibrils (PPF) to enhance the interfacial stability and structural strength of diacylglycerol (DAG) and kappa-carrageenan-based emulsion. Primarily, pea protein isolate fibrillated for 20-28 h (PPF) significantly increased the interfacial dilatational modulus. The emulsion showed smaller droplets and high yield stress at oil-water ratios of 6:4-5:5. PPF promoted DAG crystallization and the alignment of crystals at droplet surface which greatly increased the emulsion gel strength, yield stress and structure maintaining ability when subjected to high temperature. The crystallization kinetics results revealed a faster nucleation but slower growth rate mediated by the PPF which changed the crystal distribution. Molecular docking and molecular dynamics simulations confirmed that PPF molecules provided more binding amino acid sites (e.g., Leu, Asn, Arg) with DAG than PPI and adopted a more stable interfacial conformation with closer contact to the center of DAG through hydrogen bonding and hydrophobic interactions. This study reveals that the assembly of PPF with DAG showed a synergistic effect in enhancing interfacial film strength through the redistribution of lipid crystals and provides a novel strategy to fabricate emulsion gels for animal fat replacement.
The immunogenic cell death (ICD) of tumor cells generates abundant damage-associated molecular patterns (DAMPs) to induce efficient anti-tumor immune responses. However, dysregulated efferocytosis causes rapid clearance of DAMPs, thereby impeding immunotherapy progression. It has been revealed that the externalization of phosphatidylserine (PS) on apoptotic tumor cells serves as a key signal that drives efferocytosis imbalance. Here, we prepared a nanodrug HM-NP@SF&Xs, using hybrid membranes (HM) of macrophage and hepatocellular carcinoma (HCC) cell coated polymeric micelles incorporating sorafenib (SF) and Xkr8 siRNA. The HM coating prolongs blood circulating and enhances tumor targeting of nanodrugs, leading to efficient drug delivery into tumor. In addition, SF induces HCC apoptosis to trigger tumor ICD, thereby amplifying antitumor immune responses. Most importantly, the efferocytosis of SF-induced DAMPs can be effectively inhibited by Xkr8 siRNA via inhibition of PS exposure. Besides, systemic immune-related side effects of HCC cell membranes and Xkr8 siRNA are effectively reduced. In vitro and in vivo experiments demonstrated that the HM coated nanodrug elicits potent antitumor immune responses through inhibition of efferocytosis and release of inflammatory cytokines. The study provides an innovative strategy for drug delivery to HCC for enhanced immunotherapy against HCC. STATEMENT OF SIGNIFICANCE: Efferocytosis leads to the rapid clearance of immunogenic tumor debris, thereby suppressing anti-tumor immune responses. Herein, a hybrid membrane-coated nanodrug (HM-NP@SF&Xs) is developed to overcome efferocytosis-driven immunosuppression in hepatocellular carcinoma (HCC). By coating sorafenib and Xkr8 siRNA-loaded polymeric micelles with macrophage & tumor cell hybrid membrane, the platform achieves prolonged circulation and tumor-specific drug delivery. Sorafenib induces immunogenic cell death, while Xkr8 siRNA blocks phosphatidylserine externalization to inhibit efferocytosis of apoptotic tumor cells. This dual-action strategy amplifies antitumor immunity while reducing systemic side effects, offering a promising approach for enhanced cancer immunotherapy.