Evaluation of riboflavin, nanocurcumin, and hydrogen peroxide under light conditions: reduction of mature dental biofilms and enamel mineral loss.

BACKGROUND: Biofilms are a potential harbor for many microorganisms. The aim of this study was to test the efficacy of riboflavin (Rib), nano-micelle curcumin (NC), and hydrogen peroxide (HP), alone and in combination with the respective light (light-emitting diode (LED) or 980 nm diode laser) on the reduction of Streptococcus mutans and Lactobacillus acidophilus dual-species biofilms and their effect on the enamel mineral loss. MATERIALS AND METHODS: The biofilms were formed on saliva-coated enamel slabs. Then, the biofilms were treated with antimicrobial photodynamic therapy (PDT) based on LED, Rib, and NC photosensitizers and with HP also based on a 980 nm diode laser (n = 8 per group). A crystal violet assay was performed to determine the reduction of the dual-species biofilms. The enamel slabs were analyzed for calcium and phosphorus content by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). RESULTS: While HP-PDT showed a reduction of 37% (p < 0.001), PDT with NC resulted in an even greater reduction of dual-species biofilms (40%, p < 0.001) than HP- and Rib-mediated PDT. In the EDX test, no significant difference was found between the control group and the treatment groups. CONCLUSIONS: The use of natural photosensitizers such as NC in PDT has an effect that may be potentially important in reducing caries-causing bacteria.

Carrageenan-ferrocene-eicosapentaenoic acid composite hydrogel induce ferroptosis and apoptosis for anti-tumor recurrence and metastasis.

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.

Bletilla striata polysaccharide-coated andrographolide nanomicelles for targeted drug delivery to enhance anti-colon cancer efficacy.

Background: 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). Methods: 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. Results: 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. Conclusion: 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.

A Tween-80 modified hypoxia/esterase dual stimulus-activated nanomicelle as a delivery platform for carmustine - Design, synthesis, and biological evaluation.

As a clinical anti-glioma agent, the therapeutic effect of carmustine (BCNU) was largely decreased because of the drug resistance mediated by O6-alkylguanine-DNA alkyltransferase (AGT) and the blood-brain barrier (BBB). To overcome these obstacles, we synthesized a BCNU-loaded hypoxia/esterase dual stimulus-activated nanomicelle, abbreviated as T80-HACB/BCNU NPs. In this nano-system, Tween 80 acts as the functional coating on the surface of the micelle to facilitate transport across the BBB. Hyaluronic acid (HA) with active tumor-targeting capability was linked with the hypoxia-sensitive AGT inhibitors (O6-azobenzyloxycarbonyl group) via an esterase-activated ester bond. The obtained T80-HACB/BCNU NPs had an average particle size of 232.10 ± 10.66 nm, the zeta potential of -18.13 ± 0.91 mV, and it showed high drug loading capacity, eximious biocompatibility and dual activation of hypoxia/esterase drug release behavior. The obtained T80-HACB/BCNU NPs showed enhanced cytotoxicity against hypoxic T98G and SF763 cells with IC50 at 132.2 µM and 133.1 µM, respectively. T80 modification improved the transportation of the micelle across an in vitro BBB model. The transport rate of the T80-HACB/Cou6 NPs group was 12.37 %, which was 7.6-fold (p<0.001) higher than the micelle without T80 modification. T80-HACB/BCNU NPs will contribute to the development of novel CENUs chemotherapies with high efficacy.

Immune modulation of the liver metastatic colorectal cancer microenvironment via the oral CAPOX-mediated cGAS-STING pathway.

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.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.

Effect of nano-micelle curcumin on hepatic enzymes: A new treatment approach for non-alcoholic fatty liver disease (NAFLD).

Objective: 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. Materials and Methods: 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. Results: 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). Conclusion: 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.

Development and in vitro evaluation of carmustine delivery platform: A hypoxia-sensitive anti-drug resistant nanomicelle with BBB penetrating ability.

Glioma is extremely difficult to be completely excised by surgery due to its invasive nature. Thus, chemotherapy still is the mainstay in the treatment of glioma after surgery. However, the natural blood-brain barrier (BBB) greatly restricts the penetration of chemotherapeutic agents into the central nervous system. As a front-line anti-glioma agent in clinical, carmustine (BCNU) exerts antitumor effect by inducing DNA damage at the O6 position of guanine. However, the therapeutic effect of BCNU was largely decreased because of the drug resistance mediated by O6-alkylguanine-DNA alkyltransferase (AGT) and insufficient local drug concentrations. To overcome these obstacles, we synthesized a BCNU-loaded hypoxia-responsive nano-micelle with BBB penetrating capacity and AGT inhibitory activity, named as T80-HA-AZO-BG/BCNU NPs. In this nano-system, Tween 80 (T80) serves as a functional coating on the surface of the micelle, promoting transportation across the BBB. Hyaluronic acid (HA) with active tumor-targeting capability was linked with the hydrophobic O6-benzylguanine (BG) analog via a hypoxia-sensitive azo bond. Under hypoxic tumor microenvironment, the azo bond selectively breaks to release O6-BG as AGT inhibitor and BCNU as DNA alkylating agent. The synthesized T80-HA-AZO-BG/BCNU NPs showed good stability, favorable biocompatibility and hypoxia-responsive drug-releasing ability. T80 modification improved the transportation of the micelle across an in vitro BBB model. Moreover, T80-HA-AZO-BG/BCNU NPs exhibited significantly enhanced cytotoxicity against glioma cell lines with high AGT expression compared with traditional combined medication of BCNU plus O6-BG. We expect that the tumor-targeting nano-micelle designed for chloroethylnitrosourea will provide new tools for the development of effective glioma therapy.

Nanomicelle curcumin-induced testicular toxicity: Implications for altered mitochondrial biogenesis and mitophagy following redox imbalance.

The purpose of this study was to examine the effects of nano-micelle curcumin (NMC)-induced redox imbalance on mitochondrial biogenesis and mitophagy. For this purpose, 24 mature male Wistar rats were divided into control and NMC-received groups (7.5, 15, and 30 mg/kg) groups. After 48 days, the Nrf1, Nrf2, and SOD (Cu/Zn) expression levels, as well as GSH/GSSG, NADP+ /NADPH relative balances (elements involved in redox homeostasis) were analyzed. Moreover, to explore the effect of NMC on mitochondrial biogenesis, the expression levels of Mfn1, Mfn2, OPA1, Fis1, and Drp1 were investigated. Finally, the expression levels of Parkin/PARK and PINK (genes involved in mitochondrial quality control), as well as LC3-I/II (mitophagy marker), were analyzed. Observations showed that NMC, dose-dependently, altered GSH/GSSG, NADP+ /NADPH relative balances, suppressed SOD expression and diminished its biochemical level, and repressed Nrf1 and Nrf2 expression levels. Moreover, it could change the Mfn1, Mfn2, OPA1, Fis1, and Drp1 expression pattern and stimulate the Parkin/PARK and PINK as well as LC3-I/II expression levels, dose-dependently. In conclusion, chronic and high-dose NMC is able to suppress the redox capacity by down-regulating the Nrf1 and Nrf2 expression. Finally, at high-dose levels, it is able to trigger mitophagy signaling in the testicles.

Catechin-Functionalized Cationic Lipopolymer Based Multicomponent Nanomicelles for Lung-Targeting Delivery.

Catechins from green tea are one of the most effective natural compounds for cancer chemoprevention and have attracted extensive research. Cancer cell-selective apoptosis-inducing properties of catechins depend on efficient intracellular delivery. However, the low bioavailability limits the application of catechins. Herein, a nano-scaled micellar composite composed of catechin-functionalized cationic lipopolymer and serum albumin is constructed. Cationic liposomes tend to accumulate in the pulmonary microvasculature due to electrostatic effects and are able to deliver the micellar system intracellularly, thus improving the bioavailability of catechins. Albumin in the system acts as a biocompatible anti-plasma absorbent, forming complexes with positively charged lipopolymer under electrostatic interactions, contributing to prolonged in vivo retention. The physicochemical properties of the nano-micellar complexes are characterized, and the antitumor properties of catechin-functionalized materials are confirmed by reactive oxygen species (ROS), caspase-3, and cell apoptosis measurements. The role of each functional module, cationic polymeric liposome, and albumin is revealed by cell penetration, in vivo animal assays, etc. This multicomponent micellar nanocomposite has the potential to become an effective vehicle for the treatment of lung diseases such as pneumonia, lung tumors, sepsis-induced lung injury, etc. This study also demonstrates that it is a great strategy to create a delivery system that is both tissue-targeted and biologically active by combining cationic liposomes with the native bioactive compound catechins.

Bioabsorbable nano-micelle hybridized hydrogel scaffold prevents postoperative melanoma recurrence.

The residual and scattered small tumor tissue or cells after surgery are the main reason for tumor recurrence. Chemotherapy has a powerful ability to eradicate tumors but always accompanied by serious side effects. In this work, tissue-affinity mercapto gelatin (GelS) and dopamine-modified hyaluronic acid (HAD) were employed to fabricate a hybridized cross-linked hydrogel scaffold (HG) by multiple chemical reactions, which could integrate the doxorubicin (DOX) loaded reduction-responsive nano-micelle (PP/DOX) into this scaffold via click reaction to obtain the bioabsorbable nano-micelle hybridized hydrogel scaffold (HGMP). With the degradation of HGMP, PP/DOX was slowly released and formed targeted PP/DOX with degraded gelatin fragments as target molecules, which increased the intracellular accumulation, and inhibited the aggregation of B16F10 cells in vitro. In mouse models, HGMP absorbed the scattered B16F10 cells and released targeted PP/DOX to suppress tumorigenesis. For another, implantation of HGMP at the surgical site reduced the recurrence rate of postoperative melanoma and inhibited the growth of recurrent tumors. Meanwhile, HGMP significantly relieved the damage of free DOX to hair follicle tissue. This bioabsorbable nano-micelle hybridized hydrogel scaffold provided a valuable strategy for adjuvant therapy after tumor surgery.

Polymeric nano-micelle of carbon monoxide donor SMA/CORM2 ameliorates acetaminophen-induced liver injury via suppressing HMGB1/TLR4 signaling pathway.

Acetaminophen (APAP) overdose-induced hepatotoxicity is the most common cause of acute liver failure. Excessive generation of reactive oxygen species (ROS) and inflammatory responses are the major causes of necrosis and/or necroptosis of the liver cells. Currently, the treatment options for APAP-induced liver injury are very limited, N-acetylcysteine (NAC) is the only approved drug to treat APAP overdose patients. It is of great necessity to develop new therapeutic strategies. In a previous study, we focused on the anti-oxidative, anti-inflammatory signal molecule carbon monoxide (CO), and developed a nano-micelle encapsulating CO donor, i.e., SMA/CORM2. Administration of SMA/CORM2 to the mice exposed to APAP significantly ameliorated the liver injury and inflammatory process, in which modulating macrophage reprogramming plays a critical role. Along this line, in this study, we investigated the potential effect of SMA/CORM2 on toll-like receptor 4 (TLR4) and high mobility group protein B1 (HMGB1) signaling pathways that are known to be closely involved in many inflammatory responses and necroptosis. In a mouse APAP-induced liver injury model, similar to the previous study, SMA/CORM2 at 10 mg/kg remarkably improved the condition of the liver after injury as evidenced by histological examination and liver function. During the process of liver injury triggered by APAP, TLR4 expression gradually increased over time, and it was significantly upregulated as early as 4 h after APAP exposure, whereas, an increase of HMGB1 was a late-stage event. Notably, SMA/CORM2 treatment suppressed significantly both TLR4 and HMGB1, consequently inhibiting the progression of inflammation and liver injury. Compared to CORM2 without SMA modification (native CORM2) of 1 mg/kg that is equivalent to 10 mg/kg of SMA/CORM2 (the amount of CORM2 in SMA/CORM2 is 10% [w/w]), SMA/CORM2 exhibited a much better therapeutic effect, indicating its superior therapeutic efficacy to native CORM2. These findings revealed that SMA/CORM2 protects against APAP-induced liver injury via mechanisms involving the suppression of TLR4 and HMGB1 signaling pathways. Taking together the results in this study and previous studies, SMA/CORM2 exhibits great therapeutic potential for APAP overdose-induced liver injury, we thus anticipate the clinical application of SMA/CORM2 for the treatment of APAP overdose, as well as other inflammatory diseases.

Characterization and Evaluation of Rapamycin-Loaded Nano-Micelle Ophthalmic Solution.

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.

Peptide-based Nanomaterials: Self-assembly and Applications.

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.

Histopathological Evaluation of Nanocurcumin for Mitigation of Radiation- Induced Small Intestine Injury.

AIM: In the current study, we aimed to mitigate radiation-induced small intestinal toxicity using post-irradiation treatment with nano-micelle curcumin. BACKGROUND: Small intestine is one of the most radiosensitive organs within the body. Wholebody exposure to an acute dose of ionizing radiation may lead to severe injuries to this tissue and may even cause death after some weeks. OBJECTIVE: This study aimed to evaluate histopathological changes in the small intestine following whole-body irradiation and treatment with nanocurcumin. MATERIALS AND METHODS: Forty male Nordic Medical Research Institute mice were grouped into control, treatment with 100 mg/kg nano-micelle curcumin, whole-body irradiation with cobalt-60 gamma-rays (dose rate of 60 cGy/min and a single dose of 7 Gy), and treatment with 100 mg/kg nano-micelle curcumin 1 day after whole-body irradiation for 4 weeks. Afterward, all mice were sacrificed for histopathological evaluation of their small intestinal tissues. RESULTS: Irradiation led to severe damage to villi, crypts, glands as well as vessels, leading to bleeding. Administration of nano-micelle curcumin after whole-body irradiation showed a statistically significant improvement in radiation toxicity of the duodenum, jejunum and ileum (including a reduction in infiltration of polymorphonuclear cells, villi length shortening, goblet cells injury, Lieberkühn glands injury and bleeding). Although treatment with nano-micelle curcumin showed increased bleeding in the ileum for non-irradiated mice, its administration after irradiation was able to reduce radiation-induced bleeding in the ileum. CONCLUSION: Treatment with nano-micelle curcumin may be useful for mitigation of radiationinduced gastrointestinal system toxicity via suppression of inflammatory cells' infiltration and protection against villi and crypt shortening.

Analogous foliar uptake and leaf-to-root translocation of micelle nanoparticles in two dicot plants of diverse families.

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.

Nanoradiosensitizer with good tissue penetration and enhances oral cancer radiotherapeutic effect.

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.

ROS-sensitive calcipotriol nano-micelles prepared by methoxypolyethylene glycol (mPEG) - modified polymer for the treatment of psoriasis.

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.

Self-assembled nano-micelles of lactoferrin peptides: Structure, physicochemical properties, and application for encapsulating and delivering curcumin.

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.

Transcriptomics and methylomics study on the effect of iodine-containing drug FS-1 on Escherichia coli ATCC BAA-196.

Aim: Promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant Escherichia coli was demonstrated. Materials & methods: RNA sequencing for transcriptomics and the complete genome sequencing by SMRT PacBio were followed by genome assembly and methylomics. Results & conclusion: FS-1-treated E. coli showed an increased susceptibility to antibiotics ampicillin and gentamicin. Cultivation with FS-1 caused gene expression alterations toward anaerobic respiration, increased anabolism and inhibition of many nutrient uptake systems. Main targets of iodine-containing particles were cell membrane structures causing oxidative, osmotic and acidic stresses. Identification of methylated nucleotides showed an altered pattern in the FS-1-treated culture. Possible role of transcriptional and epigenetic modifications in the observed increase in susceptibility to gentamicin and ampicillin were discussed.

Lay abstract New approaches of combatting drug-resistant infections are in demand as the development of new antibiotics is in a deep crisis. This study was set out to investigate molecular mechanisms of action of new iodine-containing nano-micelle drug FS-1, which potentially may improve the antibiotic therapy of drug-resistant infections. Iodine is one of the oldest antimicrobials and until now there were no reports on development of resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of action, however, remain unclear. The collection strain Escherichia coli ATCC BAA-196 showing an extended spectrum of resistance to ßß-lactam and aminoglycoside antibiotics was used in this study as a model organism. Antibiotic resistance patterns, whole genomes and total RNA sequences of the FS-1-treated (FS) and negative control (NC) variants of E. coli BAA-196 were obtained and analyzed. FS culture showed an increased susceptibility to antibiotics associated with profound gene expression alterations switching the bacterial metabolism to anaerobic respiration, increased anabolism, osmotic stress response and inhibition of many nutrient uptake systems. Nucleotide methylation pattern were identified in FS and NC cultures. While the numbers of methylated sites in both genomes remained similar, some peculiar alterations were observed in their distribution along chromosomal and plasmid sequences.