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The assemblies of anisotropic nanomaterials have attracted considerable interest in advanced tumor therapeutics because of the extended surfaces for loading of active molecules and the extraordinary responses to external stimuli for combinatorial therapies. These nanomaterials were usually constructed through templated or seed-mediated hydrothermal reactions, but the lack of uniformity in size and morphology, as well as the process complexities from multiple separation and purification steps, impede their practical use in cancer nanotherapy. Gas-phase epitaxy, also called aerotaxy (AT), has been introduced as an innovative method for the continuous assembly of anisotropic nanomaterials with a uniform distribution. This process does not require expensive crystal substrates and high vacuum conditions. Nevertheless, AT has been used limitedly to build high-aspect-ratio semiconductor nanomaterials. With these considerations, a modified AT was designed for the continuous in-flight assembly of the cell-penetrating Fenton nanoagents (Mn–Fe CaCO3(AT) and Mn–Fe SiO2(AT)) in a single-pass gas flow because cellular internalization activity is essential for cancer nanotherapeutics. The modified AT of Mn–Fe CaCO3and Mn–Fe SiO2to generate surface nanoroughness significantly enhanced the cellular internalization capability because of the preferential contact mode with the cancer cell membrane for Fenton reaction-induced apoptosis. In addition, it was even workable for doxorubicin (DOX)-resistant cancer cells after DOX loading on the nanoagents. After combining with immune-checkpoint blockers (antiprogrammed death-ligand 1 antibodies), the antitumor effect was improved further with no systemic toxicity as chemo-immuno-chemodynamic combination therapeutics despite the absence of targeting ligands and external stimuli.

[Display omitted] • TPP-ZC-IR-PNPs specifically targeted the mitochondria and avoided lysosomes. • Zn-doped Cu NPs are effective in inducing the ROS generation upon laser irradiation. • The photothermal and photodynamic therapy synergistically induced enhanced apoptosis and tumor suppression in vivo. Chemo-resistance has pushed cancer treatment to the boundary of failure. This challenge has encouraged scientists to look for nanotechnological solutions. In this study, we have taken this goal one step further without depending on chemotherapy. Specifically, hybrid metal, polymer, and lipid nanoparticles that formed an IR780-a photosensitizer and Zinc copper oxide incorporated nanoparticle (ZCNP) nanoparticles were utilized in a combined photothermal and photodynamic therapy. Through the mediation of triphenylphosphonium (TPP) as a mitochondria-targeting moiety, TPP-conjugated polymer-lipid hybrid nanoparticles containing ZCNP/IR-780 significantly enhanced cellular uptake by cancer cells and selectively targeted the mitochondria, which improved the induction of apoptosis. In tumor-bearing mice, the nanoparticles were detected predominantly in tumors rather than in the other principle organs, which did not show notable signs of toxicity. Both in vitro and in vivo results demonstrated a great improvement in photothermal and photodynamic efficacy in combination when compared to either one individually, and a significant inhibition of tumor growth was observed with the combined therapies. In summary, this study describes an effective mitochondria-targeting nanocarrier for the treatment of cancer using combined photothermal and photodynamic therapies. [ABSTRACT FROM AUTHOR]

Cellular FLIP (cFLIP) is a crucial player of apoptosis-regulated pathways that is frequently overexpressed in solid cancers. To inhibit c-FLIP, pre- and post-transcriptionally, a multifunctional nanoparticle (NP) was created to deliver cFLIP-specific small interfering RNA (siRNA) into cancer cells. Specifically, Vorinostat (Vor)-loaded mesoporous silica nanoparticles (MSN) were conjugated with polyethylenimine-biotin (PB), followed by electrostatically binding with cFLIP siRNA (Vor/siR@MSN-PB). To stabilize and prolong the circulation time of nanoparticles, a bialdehyde-modified poly(ethylene glycol) (PEG) was cross-linked onto the polyethylenimine (PEI) backbone via the formation of the imine linkage (Schiff base) (Vor/siR@MSN-PB-PEG). The Schiff base is highly stable at physiological pH 7.4 but labile under slightly acidic pH conditions. In the acidic tumor microenvironment (TME), the PEG outer layer could be rapidly cleaved, resulting in the switching of the nanoparticle surface charge to positive, which specifically enhances internalization of the NPs to the biotin-positive tumor cells. Our results demonstrated the successful preparation of Vor/siR@MSN-PB-PEG NPs, in which the siRNA was effectively protected in serum and regulated the expression of cFlip, post-transcriptionally. The presence of the PEG layer resulted in high tumor accumulation and high efficacy in tumor inhibition, which was a result of the efficient cFLIP suppression. Furthermore, in the low-dose regimen of Vorinostat—the pre-transcriptional cFLIP suppressor, treatment with Vor/siR@MSN-PB-PEG NPs was found to be safe with the treated mice, indicating a promising combination regimen for cancer therapy.

The consolidation of nanovectors with biological membranes has recently been a subject of interest owing to the prolonged systemic circulation time and delayed clearance by the reticuloendothelial system of such systems. Among the different biomembranes, the macrophage membrane has a similar systemic circulation time, with an additional chemotactic aptitude, targeting integrin proteins. In this study, we aimed to establish a laser-activated, disintegrable, and deeply tumor-penetrative nanoplatform. We used a highly tumor-ablative and laser-responsive disintegrable copper sulfide nanoparticle, loaded it with paclitaxel, and camouflaged it with the macrophage membrane for the fabrication of PTX@CuS@MMNPs. The in vitropaclitaxel release profile was favorable for release in the tumor microenvironment, and the release was accelerated after laser exposure. Cellular internalization was improved by membrane encapsulation. Cellular uptake, cytotoxicity, reactive oxygen species generation, and apoptosis induction of PTX@CuS@MMNPs were further improved upon laser exposure, and boosted permeation was achieved by co-administration of the tumor-penetrating peptide iRGD. In vivotumor accumulation, tumor inhibition rate, and apoptotic marker expression induced by PTX@CuS@MMNPs were significantly improved by laser irradiation and iRGD co-administration. PTX@CuS@MMNPs induced downregulation of cellular proliferation and angiogenic markers but no significant changes in body weight, survival, or significant toxicities in vital organs after laser exposure, suggesting their biocompatibility. The disintegrability of the nanosystem, accredited to biodegradability, favored efficient elimination from the body. In conclusion, PTX@CuS@MMNPs showed promising traits in combination therapies for excellent tumor eradication.

As well as the exploration of translatable delivery nanosystems for cancer therapeutic agents, the development of automatable continuous-flow manufacturing technology comprising digitally controlled reactions for the on-demand production of pharmaceuticals is an important challenge in anticancer nanomedicine. Most attempts to resolve these issues have involved the development of alternative reactions, formulations, or constructs containing stimulus components aimed at producing multiple approaches for highly efficacious combination cancer therapies. However, there has been no report of a platform based on plug-in execution that enables continuous-flow manufacture in a compact, reconfigurable manner, although an optimal platform technology may be a prerequisite for the timely translation of recently developed nanomedicines. To this end, we describe the development of a platform toward digitizable, continuous manufacture by a serial combination of plug-in reactionwares (heating plates, a spraying cup, and a photochamber) for single-pass flow fabrication. Specifically, we fabricated three different composite nanoblocks consisting of Au1Ag9(<8 nm; stimulus component), docetaxel (an anticancer drug), and bovine serum albumin (a protective and targeting agent) using our system, with the result of producing nanoblocks with photothermally modulatable and structurally disintegratable properties. These were examined for effectiveness in near-infrared-induced chemothermal cancer therapy and renal excretion of Au1Ag9particles and exhibited high anticancer efficacy and warrantable biosafety.

Background: The alleviating effects of diabetic nephropathy and hepatopathy of β-glucan were evaluated in this study. Objective: The anti-diabetic effects of β -glucan from Aureobasidium pullulans were assessed in a streptozotocin (STZ)-induced rat diabetes model at 62.5 and 125 mg/kg doses. In addition, the possibility of changes in the effects of β-glucan according to the severity of diabetes was also assessed at one dosage (62.5 mg/kg): severe, >360 mg/dL; slight, 130-200 mg/dL. Methods: Test articles were administered orally to STZ-induced diabetic rats from 21 days after STZ dosing for 4 weeks. Each of five or six female rats per group was selected using blood glucose levels at 21 days after STZ dosing. Changes in body weight were recorded during the study, along with blood glucose, blood urea nitrogen, creatinine, and serum aspartate aminotransferase and alanine aminotransferase levels. On the day of sacrifice, livers and kidneys were weighed and observed microscopically for changes in the percentage of degenerative regions and numbers of degenerative tubules in the kidney. Results: β-glucan showed no hypoglycemic effects in the STZ-induced diabetic rat model. However, it had favorable effects on decreasing diabetic complications related to diabetic nephropathy and hepatopathy. Conclusion: Based on the results of this study, it was concluded that β-glucan showed favorable effects in decreasing diabetic complications in STZ-induced rat diabetes model.

While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs, the outcomes often exhibit suboptimal particle size distribution and large particle sizes, limiting their effectiveness. In this study, we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs, enabling the fabrication of nanoparticles with fine and uniform particle size distribution. Regorafenib (1 g), as a model drug, copovidone (5 g), and sodium dodecyl sulfate (0.1 g) were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer. The electrostatic spray-dried nanoparticles (ESDN) showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles (CSDN). ESDN demonstrated significantly enhanced solubility and rapid release in water. In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent, exhibiting superior cytotoxicity compared to CSDN. Furthermore, ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN. These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs, effectively addressing the limitations associated with CSD methods.

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(β-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.

Metformin (MET) is a common treatment for type II diabetes. Here, we demonstrate the anticancer activity of a polymeric metformin derivative. We successfully synthesized the polypeptide (poly-l-lysine [PLL]) derivative of metformin (LysMET) and demonstrated its capacity as an anticancer therapeutic and gene carrier. miRNA-320a was loaded into the cationic LysMET and enveloped in a lipid bilayer, and a MUC1-specific aptamer was conjugated to the surface (A-Lipo@mLysMET). The LysMET-containing guanidine moiety was more tolerable than the secondary amine-containing PLL. LysMET showed similar efficacy to MET in the induction of HT-29 tumor suppression, indicating the importance of the biguanide moiety. The synergistic effect of miRNA-320a and LysMET treatment significantly decreased cell viability compared with LysMET treatment alone, which was attributed to the role of miRNA in the β-catenin pathway. A-Lipo@mLysMET showed excellent antitumor efficacy and significantly reduced the tumor burden in all groups. AMPKα phosphorylation was markedly increased by LysMET compared with the control, with significant inhibition of the mTOR pathway. The TUNEL assay showed that apoptosis was the main mechanism responsible for cancer cell death and that A-Lipo@mLysMET resulted in the highest proportion of TUNEL-positive cells (∼36%). No noticeable organ damage was observed after treatment with either LysMET or A-Lipo@mLysMET, confirming the excellent safety profile of guanide-modified polymers. Overall, we demonstrated the feasibility of LysMET for the effective control of tumor progression as well as its dual role, as both a drug and a gene carrier.

Cell-based delivery platforms have received great interest in recent years and have been indicated as a promising strategy for cancer immunotherapy. Despite their wide applications in the clinical and preclinical stages, their concomitant viability and efficacy remain major issues. Herein, a strategy for harnessing regulatory T (Treg) cells is developed as an actively targeting drug-delivery system to transport drug-loaded liposomes to the desired tumor sites via conjugating liposomes on the surface of Treg cells. Under the guidance of tumor-oriented chemokines, liposome-anchored Treg cells can be leveraged to migrate and infiltrate the acidic tumor microenvironment, where pH-sensitive liposomes release the loaded cargos [comprising interleukin-2, programmed cell death ligand 1 antibody (PD-L1), and imiquimod], provoke dramatic dendritic cell maturation, block the PD-1/PD-L1 immune-checkpoint, elevate the frequency of infiltrating CD8+effector T cells, and collectively contribute to potent inhibition of in situ and metastatic tumors. Here, the findings suggest a potential approach that offers a simple, robust, and safe insight into the tuning of Treg cells as an encouraging vector for augmenting cancer immunotherapy.

Inorganic nanomaterial (INM)-based combination cancer therapies have been extensively employed over the past two decades because of their benefits over traditional chemo- and radiotherapies. However, issues regarding the toxicity and accumulation of INMs in the body have arisen. This problem may be improved through the use of biodegradable or disintegrable nanosystems such as black phosphorus (BP). Challenges to the manufacture of fully nanodimensional BP remain. In addition, improvements in recently developed cancer immunotherapies require their incorporation with drugs, targeting agents, and delivery vehicles. With these needs in mind, this study develops a method for instant in-flight manufacture of nanodimensional BP using plug-and-play devices for subsequent assembly of photoimmunotherapeutic core@shell composites containing mutated B-raf inhibitors (dabrafenib), immune checkpoint inhibitors (PD-L1), and cancer-targeting antibodies (CXCR4). The resulting nanocomposites exhibited cancer targetability and regulatability of PD-L1 expression both in vitro and in vivo. These activities were further increased upon near-infrared irradiation due to the incorporation of a phototherapeutic component. These results suggest that these nanocomposites are promising as a new class of advanced cancer therapeutic agents.

To investigate the enhancement of alcohol metabolism by two ginseng berry (GB) extracts and their two types of mixed herbal beverages through in vitroand in vivoexperiments. Two GB extract solutions and their two herbal beverages were evaluated as enhancers of alcohol metabolism in normal human embryonic liver cells (CL-48 cell line) through assays of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity. Cytotoxicity was also assessed in the same cell line using an MTT assay. Effects on alcohol metabolism were also observed in vivothrough measurement of serum alcohol, acetaldehyde, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in alcohol treated rats. Blood samples were serially collected at 1, 2, 3, 4, 6 and 8 hrs after a single ethanol (EtOH) treatment. A single treatment with the test samples was administered orally 30 minutes after EtOH treatment. GB extract solutions effectively elevated the ADH and ALDH activity observed in vitro, while no treatment- related cytotoxic effects were found with test samples t concentrations up to 100 mg/mL. Significantly lower (p<0.01 or p<0.05) serum alcohol and acetaldehyde content was observed in samples from treated rats than in those from control rats (EtOH only) 1 or 2 hrs after EtOH treatment. In addition, noticeable decreases were observed in serum AST and ALT levels in treated samples 8 hrs after EtOH administration. HM40, an herbal mixture containing GB extract (40 mg/75 mL of ginsenoside Re), showed betters enhancement of alcohol metabolism through ADH/ALDH activation, as well as related hepatoprotective effects. GB extracts effectively enhanced alcohol metabolism without cytotoxicity while also providing possible hepatoprotective effects that could serve as a functional ingredient in anti-hangover alternative therapies. These extracts are expected to be more effective when made into herbal mixture beverages.

Conjugatable nanobimetals exhibiting broadband light absorption for use as phototherapeutic platforms were assembled via a plug-and-play continuous gas flow route. Electrically produced AuCu nanobunches (NBs) under nitrogen gas flow were directly injected into cysteine (cys) solution through gas pressurization to mechanically spray the solution (AuCu into cys droplets). The sprayed droplets were then exposed to 185 nm UV light (higher photon energy [6.2 eV] than the work functions of Au [5.1 eV] and Cu [4.7 eV]) to initiate photoionization of AuCu NBs for subsequent electrostatic reaction with the SH–group of cys to form cys-inserted AuCu (AuCu-cys) platforms in a single-pass gas stream. These platforms exhibited broadband light absorption spectra because of hybridized interparticle plasmonic coupling and could be conjugated to folic acid (FA) when dispersed in FA solution to form highly dispersible, biocompatible, and cancer-targetable AuCu-cys-FA. This material was suitable for use in targeted phototherapy of folate-receptor (FR)-rich cancers via FR-mediated endocytosis, and loading doxorubicin (DOX) into AuCu-cys-FA (i.e., AuCu-cys-DOXFA) facilitated chemo-phototherapy because of photoresponsive anticancer drug release upon induction of hyperthermia.

Folate-targeting self-assembled nanoparticles (NPs) using biocompatible and biodegradable natural polymers chitosan (Cs) and chondroitin sulfate (Chs) were developed to address the major challenge in cancer treatment, the selective delivery of nanoparticles to the target site. In this study, we successfully incorporated a hydrophobic drug, bortezomib (Bor), into folic acid (FA)-conjugated Cs/Chs self-assembled NPs (Bor/Cs/Chs-FA) for colorectal cancer therapy. The particle size and polydispersity index of Bor/Cs/Chs-FA were ∼196.5 ± 1.2 nm and ∼0.21 ± 0.5, respectively. A pH-dependent release profile was observed, facilitating cancer cell-targeted drug release under an acidic tumor microenvironment. Moreover, in vitrodata revealed enhanced cellular uptake and apoptosis in folate receptor-expressing colorectal cancer cells (HCT-116 and HT-29) as compared to that in lung cancer cells (A549), which do not express folate receptors. Furthermore, intravenous administration of Bor/Cs/Chs-FA in a HCT-116 bearing xenograft mouse model showed that the NPs were a safe and effective drug delivery system. The results suggest that folate-targeted nanoparticle can be effectively applied for efficient chemotherapy of colorectal cancer.

Because of their extraordinary physical properties and biocompatibility, black phosphorus (BP) nanosheets (NSs) have been intensively employed in chemo-phototherapies, such as plasmonic inorganic nanoparticles or graphene NSs, over the past few years. However, most biomedical studies using BP NSs are only concerned with the optical property of BP NSs to repeatedly demonstrate chemo-phototherapeutic efficacies, although BP NSs have different properties from inorganic nanoparticles or graphene NSs, such as corrugated crystal structure, hydrophilicity, and biodegradability. Moreover, it is still a challenging issue to efficiently fabricate uniform BP NSs for clinical translation because of the top-down nature of fabrication, despite the easy preparation of coarse BP flakes. It is thus essential to explore their most suitable bioapplications as well as suggest an easy-to-access strategy to produce uniform BP NSs for realization as advanced therapeutic materials. To rationalize these issues, this report introduces a plug-and-play nanorization, ultrasonic bubble bursting, of coarse BP flakes for continuous BP NS production, and the resulting uniform NSs (∼40 nm lateral dimension, ∼0.15 polydispersity index) were used as base materials to load drug (doxorubicin), targeting agent (chitosan–polyethylene glycol), and cancer growth inhibitor (programmed death ligand 1 and small interfering RNA) for achieving efficacious chemo-photoimmunotherapy of colorectal cancer.

Cellular Fas-associated protein with death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP), often strongly expressed in numerous cancers, plays a pivotal role in thwarting apoptosis and inducing chemotherapy resistance in cancer. An integrated approach combining chemotherapy with suppression of c-FLIP levels could prove paramount in the treatment of cancers with c-FLIP overexpression. In this study, we utilized a polymeric layer-by-layer (LbL) assembly of silica-supported mesoporous titania nanoparticles (MTNst) to co-deliver paclitaxel (PTX) and microRNA 708 (miR708) for simultaneous chemotherapy and c-FLIP suppression in colorectal carcinoma. The resulting LbL miR708/PTX-MTNst showed dose-dependent cytotoxicity in HCT-116 and DLD-1 colorectal carcinoma cell lines, which was remarkably superior to that of free PTX or LbL PTX-MTNst. LbL miR708/PTX-MTNst strongly inhibited c-FLIP expression and resulted in increased expression of proapoptotic proteins. In DLD-1 xenograft tumor-bearing mice, the nanoparticles accumulated in the tumor, resulting in remarkable tumor regression, with the PTX and miR708-loaded nanoparticles showing significantly greater inhibitory effects than the free PTX or PTX-loaded nanoparticles. Immunohistochemical analyses of the tumors further confirmed the remarkable apoptotic and antiproliferative effects of the nanoparticles, whereas organ histology reinforced the biocompatibility of the system. Therefore, the LbL miR708/PTX-MTNst system, owing to its ability to deliver both chemotherapeutic drug and inhibitory miRNA to the tumor site, shows great potential to treat colorectal carcinoma in clinical settings.

Background: The hypoglycaemic effects of β-glucan (BG) extracts from some mushrooms and Folium mori (FM) have been reported. Objective: To determine the most effective composition of combined β-glucan originated from Aureobasidium and Folium mori extract (BGFM) for treating diabetes and complicated hepatopathy and nephropathy using streptozotocin (STZ)-induced diabetic rats. Method: Six days after STZ dosing, rats (n = 5 per group) were selected based on body weight and blood glucose levels. BGFM was orally administered once a day for 28 days (Qd × 28), and changes in blood glucose levels, body weight, liver and kidney weight, and levels of serum Blood Urea Nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured. Results: The diabetic control group exhibited dramatic decreases in body weight, and increase in liver and kidney weight, and blood glucose, serum BUN, creatinine, AST, and ALT levels compared to the non-diabetic sham group. However, these hyperglycaemic changes were markedly reduced in the Folium mori extract single group (S-FM) and some groups that received a mixed composition. Additionally, the changes related to the complicated hepatopathy and nephropathy of body weight were attenuated in the β-glucan single (S-BG) and some mixed groups compared to the diabetic control group. The anti-diabetic effects of β-glucan composition increased with its dose, and similarly, the hypoglycaemic effects of FM composition increased with its dose. Of the 11 types of mixed composition and single formulations, the BG:FM 1:4 composition was considered most effective for dual efficacy in terms of its hypoglycaemic and anti-diabetic effects. Conclusion: The greatest synergistic effects of the BGFM complex in treating the hyperglycaemic and complicated hepatopathy and nephropathy of STZ were obtained using a BG:FM 1:4 ratio.

Cancer remains a leading cause of death. A combination of anticancer agents can effectively kill cancer through multiple pathways; however, improvements to their delivery are needed. Hence, docetaxel and cisplatin-loaded liquid crystalline nanoparticles with folic acid were prepared for effective and targeted anticancer therapy. Notably, hydroxypropyl-β-cyclodextrin/cisplatin complexes in 0.9% NaCl solution were used for the prevention of possible aquation of cisplatin, which would otherwise lead to severe adverse effects. The optimized nanoparticles exhibited small particle size, high drug loading capacity (>90%), and controlled drug release profiles. In vitrocell cytotoxicity assays demonstrated that the optimized nanoparticles were taken up by folate receptor-expressing cells to a greater extent than non-folate expressing cells, which is attributable to folate-specific endocytosis of the optimized nanoparticles. Enhanced expression of apoptotic markers (Bax, p21, and cleaved caspase-3) along with enhanced anti-migration effects in MDA-MB-231 cells following treatment suggests that the optimized nanoparticles provide an effective treatment for metastatic breast cancer. These results were further supported by in vivofindings obtained for a MDA-MB-231 tumor xenograft model. Altogether, the optimized nanoparticles may potentially be developed as an effective treatment modality for folate-targeted metastatic breast cancer treatment.

Alcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury.

This study evaluated the effects of Polycan, a β-glucan produced by Aureobasidium pullulansSM-2001, on calcium (Ca) bioavailability in an ovariectomy (OVX) model and a thyroparathyroidectomy (TPTX) model of osteoporosis in the SD rat. Polycan (62.5, 125, and 250 mg/kg body weight) was administered daily with an oral gavage for 4 weeks in both the OVX group (beginning 10 weeks following OVX surgery) and the TPTX group (beginning 4 days following TPTX surgery) while a commercial food product containing 1% milk-borne Ca was available ad libitum. After 4 weeks of Polycan administration, all animals were sacrificed and changes in bone mineral density (BMD) in the femur, tibia, and lumbar vertebrae (L6) were analyzed using dual-energy X-ray absorptiometry. Ca intake was calculated based on the amount of food intake during the 24 h period prior to sacrifice and the Ca balance, absorption, and retention ratios were calculated based on Ca intake, urinary and faecal Ca content, and Ca balance. Polycan treatment resulted in a marked increase in the BMD of the femur, tibia, and L6relative to the OVX and TPTX controls with concomitant increases in Ca bioavailability and decreases in secreted Ca. These findings indicate that Polycan may enhance the absorption and bioavailability of Ca and improve Ca balance.

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caeruleaL., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency.

The present study was performed to evaluate the laxative effects of fermented rice extract (FRe) in normal rats. FRe was orally administered at doses of 100, 200, and 300 mg/kg once per day for 15 days, and the changes in fecal parameters (fecal pellet numbers, weights, and water contents), gastrointestinal transit ratio, fecal mucus contents, colonic mucus-producing cell numbers, and mean colonic mucosa thicknesses were examined in normal rats. The laxative effects of FRe were compared with those of sodium picosulfate. At the three doses administered, FRe treatment resulted in marked increases in fecal pellet numbers and water contents discharged over 24 h, surface mucus thickness in the colonic lumen, intestinal charcoal-transit ratio, and in thickness and mucus-producing goblet cell number of the colonic mucosa with decreases in fecal pellet numbers and mean diameters remaining in the colonic lumen in comparison to the vehicle control. With the exception of intestinal charcoal-transit ratio, the effects of FRe were less marked than those of sodium picosulfate. The results of this study suggest that FRe has a laxative effect without causing diarrhea, as compared with sodium picosulfate, and FRe may be highly effective as a complementary medicine in humans suffering from lifestyle-induced constipation.

It was evaluated the synergistic effects of fermented rice extracts (FRe) on the laxative and probiotic effects of yogurt in normal rats. Commercial liquid yogurt (Bulgaris™) containing 0.05%, 0.10%, and 1.0% FRe (BFRe) was administered orally to normal rats daily for 10 days. Compared with the vehicle control, the three BFRe treatments exhibited highly significant increases in fecal pellet numbers, water content, thickness of surface mucous in the colonic lumen, intestinal charcoal transit ratio, thickness of the colonic mucosa, and mucous-producing goblet cells; decreased numbers and mean diameters of fecal pellets remaining in the colonic lumen were detected compared with the vehicle control, and numbers of viable Lactobacilliin cecum contents and feces were dramatically higher than those in vehicle control rats. More favorable probiotic and laxative effects were detected in rats treated with 0.1% and 1.0% BFRe compared with equal doses of liquid yogurt or FRe alone. Therefore, appropriate concentrations of BFRe may be highly effective for alleviating constipation and provide a complementary natural approach to reducing lifestyleinduced constipation.

In this study, a novel hybrid bilayer wound dressing (HBD) has been developed for delivering a thermally unstable probiotic, Lactobacillus brevis. The HBD was composed of two layer, a hydrocolloid layer and a Lactobacillus brevis-loaded hydrogel layer as a block supporter and drug carrier, respectively. Moreover, various probiotic-loaded hydrogel layers in HBD were prepared with polyvinyl alcohol (PVA) and numerous hydrophilic polymers viaa freezing and thawing method, and their mechanical property, release and wound recovery were assessed. Among the hydrophilic polymers investigated, copovidone most improved the mechanical strength, swelling ability, and release properties; and thus, copovidone/PVA (ratio of 1.0/10) was determined as an appropriate composition of hydrogel layer in HBD. The selected HBD exhibited superior stability than conventional dressing, maintaining approximately 90% of Lactobacillus brevis(9.0 × 108CFU) during the preparation and storage process. Moreover, the HBD had about 5- and 4-fold better swelling ability and elasticity compared to the conventional dressing. Additionally, it exhibited superior recovery efficacy than the commercial dressing in the animal study. Therefore, this HBD system for delivering a thermally unstable Lactobacillus breviswould be a promising wound dressing with excellent mechanical property and wound recovery.