The immune-suppressive microenvironment of solid tumors is a key factor limiting the effectiveness of immunotherapy, which seriously threatens human life and health. Ferroptosis and apoptosis are key cell-death pathways implicated in cancers, which can synergistically activate tumor immune responses. Here, we developed a multifunctional composite hydrogel (CE-Fc-Gel) based on the self-assembly of poloxamer 407, cystamine-linked ιota-carrageenan (CA)-eicosapentaenoic acid (EPA), and ferrocene (Fc). CE-Fc-Gel improved targeting in tumor microenvironment due to its disulfide bonds. Moreover, CE-Fc-Gel promoted lipid peroxidation, enhanced reactive oxygen species (ROS) production, and decreased glutathione peroxidase 4 (GPX4), inducing ferroptosis by the synergistic effect of Fc and EPA. CE-Fc-Gel induced apoptosis and immunogenic cell death (ICD), thereby promoting dendritic cells (DCs) maturation and T cell infiltration. As a result, CE-Fc-Gel significantly inhibited primary and metastatic tumors in vivo. Our findings provide a novel strategy for enhancing tumor immunotherapy by combining apoptosis, ferroptosis, and ICD.

UNASSIGNED: Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG).
UNASSIGNED: BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test.
UNASSIGNED: In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1-24 h). What\'s more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG.
UNASSIGNED: The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.

We evaluated modulation of the immunosuppressive tumor microenvironment in both local and liver metastatic colorectal cancer (LMCC), focusing on tumor-associated macrophages, which are the predominant immunosuppressive cells in LMCC. We developed an orally administered metronomic chemotherapy regimen, oral CAPOX. This regimen combines capecitabine and a nano-micelle encapsulated, lysine-linked deoxycholate and oxaliplatin complex (OPt/LDC-NM). The treatment effectively modulated immune cells within the tumor microenvironment by activating the cGAS-STING pathway and inducing immunogenic cell death. This therapy modulated immune cells more effectively than did capecitabine monotherapy, the current standard maintenance chemotherapy for colorectal cancer. The macrophage-modifying effect of oral CAPOX was mediated via the cGAS-STING pathway. This is a newly identified mode of immune cell activation induced by metronomic chemotherapy. Moreover, oral CAPOX synergized with anti-PD-1 antibody (αPD-1) to enhance the T-cell-mediated antitumor immune response. In the CT26. CL25 subcutaneous model, combination therapy achieved a 91 % complete response rate with a confirmed memory effect against the tumor. This combination also altered the immunosuppressive tumor microenvironment in LMCC, which αPD-1 monotherapy could not achieve. Oral CAPOX and αPD-1 combination therapy outperformed the maximum tolerated dose for treating LMCC, suggesting metronomic therapy as a promising strategy.

UNASSIGNED: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes with no consumption of alcohol. Recently, curcumin is a natural polyphenol found in turmeric has been examined for the treatment of NAFLD. This study aimed to assess the efficacy of 160 mg/day nano-micelle curcumin on the amelioration of NAFLD by measuring liver enzymes.
UNASSIGNED: Patients with NAFLD were randomly divided into curcumin (intervention group n=33) and placebo (n=33) groups and at the end of the study, the data of 56 participants who completed the 2-month intervention were analyzed. Laboratory tests and questionnaires were used to gather information. Both groups received recommendations for lifestyle modification, and were advised to other necessary advices. Patients in the curcumin group received 160 mg/day of nano-micelle curcumin in two divided doses for 60 days. The 2 groups were followed up for two months and clinical and laboratory indices were compared.
UNASSIGNED: Our data showed a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the curcumin group (p<0.01) as well as a significant difference between the groups before and after the intervention in curcumin group (p<0.05). Interestingly, a meaningful decrease in AST serum level was observed in the intervention group (p<0.01).
UNASSIGNED: Our study demonstrated that short-term supplementation with nano-micelle curcumin results in the reduction of AST and ALT and is beneficial for the treatment of NAFLD.

Rapamycin-loaded nano-micelle ophthalmic solution (RAPA-NM) offers a promising application for preventing corneal allograft rejection; however, RAPA-NM has not yet been fully characterized. This study aimed to evaluate the physicochemical properties, biocompatibility, and underlying mechanism of RAPA-NM in inhibiting corneal allograft rejection. An optimized RAPA-NM was successfully prepared using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer as the excipient at a PVCL-PVA-PEG/RAPA weight ratio of 18:1. This formulation exhibited high encapsulation efficiency (99.25 ± 0.55%), small micelle size (64.42 ± 1.18 nm), uniform size distribution (polydispersity index = 0.076 ± 0.016), and a zeta potential of 1.67 ± 0.93 mV. The storage stability test showed that RAPA-NM could be stored steadily for 12 weeks. RAPA-NM also displayed satisfactory cytocompatibility and high membrane permeability. Moreover, topical administration of RAPA-NM could effectively prevent corneal allograft rejection. Mechanistically, a transcriptomic analysis revealed that several immune- and inflammation-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the downregulated genes in the RAPA-NM-treated allografts compared with the rejected allogenic corneal grafts. Taken together, these findings highlight the potential of RAPA-NM in treating corneal allograft rejection and other ocular inflammatory diseases.

Bio-inspired nanoparticles, including metallic, micelles, and polymeric, have been explored as a novel tool in the quest for effective and safe agrochemicals. Although nanoparticles (NPs) are being rapidly investigated for their usefulness in agricultural production and protection, little is known about the behaviour and interaction of oil-in-water micelle nanoparticles or nano-micelles (NM) with plants. We loaded a bio-based resin inherent of tree from the Pinaceae family as active material and produced stable nano-micelles using a natural emulsifier system. Here, we show that foliar-applied nano-micelle can translocate in two dicot plants belonging to diverse families (Coriandrum sativum -Apiaceae and Trigonella foenumgraecum -Fabaceae) via similar mode. Fluorescent-tagged NM (average diameter 11.20nm) showed strong signals and higher intensities as revealed by confocal imaging and exhibited significant adhesion in leaf compared to control. The NM subsequently translocates to other parts of the plants. As observed by SEM, the leaf surface anatomies revealed higher stomata densities and uptake of NM by guard cells; furthermore, larger extracellular spaces in mesophyll cells indicate a possible route of NM translocation. In addition, NM demonstrated improved wetting-spreading as illustrated by contact angle measurement. In a field bioassay, a single spray application of NM offered protection from aphid infestation for at least 9 days. There were no signs of phytotoxicity in plants post-application of NM. We conclude that pine resin-based nano-micelle provides an efficient, safe, and sustainable alternative for agricultural applications.

Low dose non-toxic disulfide cross-linked micelle (DCM) encapsulated paclitaxel (PTX) was found to be highly efficacious as a radiosensitizer against oral cancer preclinical model. Intensity-modulated radiation therapy was locally administered for three consecutive days 24 h after intravascular injection of DCM-[PTX] at 5 mg/kg PTX. DCM-[PTX] NPs combined with conventional radiotherapy (2 Gy) resulted in a 1.7-fold improvement in therapeutic efficacy compared to conventional PTX plus radiotherapy. Interestingly, we found that radiotherapy can decrease tight junctions and increase the accumulation of DCM-[PTX] in tumor sites. Stereotactic body radiotherapy (SBRT) given at 6 Gy was used to further investigate the synergistic anti-tumor effect. Tumor tissues were collected to analyze the relationship between the time interval after SBRT and the biodistribution of the nanomaterials. Compared to combination DCM-[PTX] with conventional radiation dose, combination DCM-PTX with SBRT was found to be more efficacious in inhibiting tumor growth.

The self-assembly behavior of polypeptides is common in nature. Compared with monopeptides, polypeptide-based self-assembled nanomaterials with ordered structures have good thermal stability, mechanical stability, semi-conductivity, piezoelectric and optical properties. In recent years, the self-assembly of polypeptides has become a hot topic in the material science and biomedical field. By reasonably adjusting the molecular structure of the polypeptide and changing the external environment of the polypeptide, the polypeptide can be self-assembled or triggered by non-covalent bonding forces such as hydrogen bond, hydrophobicity, and π - π accumulation to form specific polypeptide assemblies such as nanoparticles, hydrogels, nanofibers, and micelles. Due to good biocompatibility and controllable degradability, polypeptide-based self-assembled nanomaterials have been widely used in the fields of nanotechnology, imaging technology, biosensor, and biomedical science. As a new drug delivery system, the polypeptide-drug conjugate has the advantages of low toxicity, high efficiency, enhanced drug stability, and avoiding side effects. This paper reviews the research progress of polypeptide-drug self-assembly nanostructure in recent years. Several structural models of polypeptide self-assembly technology and the mechanism of polypeptide self-assembly are introduced. Then the assembly form of polypeptide-drug self-assembly and the application of selfassembly compound therapy is described.

Oxidative stress due to excessive reactive oxygen species (ROS) production in the skin microenvironment is one of the main mechanisms in psoriasis pathogenesis. A nano drug delivery system based on ROS-responsive release can enhance drug release at the target site. In this study, a ROS-sensitive material methoxypolyethylene glycol-thioether-thiol (mPEG-SS) was synthesized using mPEG as the parent structure with sulfide structural modification. An mPEG-SS-calcipotriol (mPEG-SS-CPT, PSC) nano-micelle percutaneous delivery system was prepared by encapsulating CPT. A small animal imaging system was used to study PSC\'s the ROS-sensitive drug release process. It is shown that endogenous ROS mainly affects PSC and releases drugs. Finally, the therapeutic effect of PSC on psoriasis was explored by animal experiments. Ultimately, it ameliorates imiquimod-induced psoriasis-like inflammation. Overall, PSC is an effective ROS-sensitive transdermal drug delivery system that is expected to provide a new strategy for treating psoriasis.

Food-derived protein hydrolysate exhibits good bioactivity, compatibility, and low toxicity, etc. However, the information on protein hydrolysate-based micelles and their application as carriers for hydrophobic bioactive compounds is limited. In this study, an enzymatic partially hydrolyzed lactoferrin hydrolysate nano-micelle with the size within 50 nm was constructed, and its formation mechanism and delivery characteristics for curcumin (Cur) were studied. The results demonstrated that Cur was loaded into the micelles through hydrophobic interaction, and the encapsulation rate of Cur by nano-micelles was (93.44 ± 0.01)%. In addition, the nano-micelle system demonstrated excellent thermal stability, dilution stability, and storage stability. The in vitro simulated digestion proved that self-assembled nano-micelles could improve the transformation rate and bioaccessibility of Cur. This study revealed that lactoferrin hydrolysate self-assembled nano-micelle is a promising delivery system for hydrophobic bioactive compounds.