Biodegradable Hypocrellin B nanoparticles coated with neutrophil membranes for hepatocellular carcinoma photodynamics therapy effectively via JUNB/ROS signaling.

Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant common liver cancer, and a major cause of death. Some natural products have been found to be used as photosensitizers in photodynamic therapy of HCC. Due to its specific molecular structure diversities and biological activities, current status of HCC treatment with nature production remains unsatisfactory, owing largely to the toxicity, side effect and inefficiency to drug targeting. Herein, we show a nanoparticle-based broad-spectrum anti-inflammatory strategy that naïve neutrophil membrane-coated PLGA nanoparticles (NM-HB NPs) were constructed for synchronous nearinfrared fluorescence (NIR FL) imaging and photodynamic therapy (PDT) for HCC. Moreover, NM-HB NPs inhibited the expression of JUNB and promoted the ROS production. JUNB depletion enhanced the anti-HCC effect of NM-HB NPs. Importantly, it was shown that NM-HB NPs are well targeted to the tumor site and overcomes the blood circulation and immune elimination in vivo and vitro. In a mouse model of HCC, the neutrophil membrane-coated nanoparticles (NM-HB NPs) show significant therapeutic efficacy by PDT and suppressing tumor tissue increase. All results demonstrated that NM coated HB NPs representing a viable and effective treatment option for HCC.

Natural-Origin Hypocrellin-HSA Assembly for Highly Efficient NIR Light-Responsive Phototheranostics against Hypoxic Tumors.

Tumor hypoxia severely limits the therapeutic efficacy of solid tumors in photodynamic therapy. One strategy is to develop photosensitizers with simultaneously high efficiency in photodynamic (PDT) and photothermal therapies (PTT) in a single natural-origin phototheranostic agent to overcome this problem. However, less attention has been paid to the natural-origin phototheranostic agent with high PDT and PTT efficiencies even though they have negligible side effects and are environmentally sustainable in comparison with many reported phototheranostic agents. In addition, almost all clinical applied photosensitizers are of natural origin so far. Herein, we synthesized a natural product-based hypocrellin derivative (AETHB), with a high singlet oxygen quantum yield of 0.64 as an efficient photosensitizer different from commercially available porphyrin-based photosensitizers. AETHB is further assembled with human serum albumin to construct nanoparticles (HSA-AETHB NPs) with a high photothermal conversion efficiency (more than 50%). As-prepared HSA-AETHB NPs have shown good water solubility and biocompatibility, pH and light stability, wide absorption (400-750 nm), and NIR emission centered at 710 nm. More importantly, HSA-AETHB NPs can be applied for fluorescent/photoacoustic dual-mode imaging and simultaneously highly efficient PDT/PTT in hypoxic solid tumors. Therefore, this natural-origin multifunctional phototheranostic agent is showing very promising for effective, precise, and safe cancer therapy in clinical applications.

Development of An Oral Treatment with the PPAR-γ-Acting Cannabinoid VCE-003.2 Against the Inflammation-Driven Neuronal Deterioration in Experimental Parkinson's Disease.

In a recent study, we described the neuroprotective properties of VCE-003.2-an aminoquinone derivative of the non-psychotropic phytocannabinoid cannabigerol (CBG)-administered intraperitoneally (i.p.) in an inflammatory model of Parkinson's disease (PD). We also demonstrated that these properties derive from its activity on the peroxisome proliferator-activated receptor-γ, in particular at a regulatory site within this receptor type. In the present study, we wanted to further confirm this neuroprotective potential using an oral lipid formulation of VCE-003.2, developed to facilitate the clinical development of this phytocannabinoid derivative. To this end, we evaluated VCE-003.2, administered orally at two doses (10 and 20 mg/kg), to mice subjected to unilateral intrastriatal injections of lipopolysaccharide (LPS), a classic model of inflammation-driven neuronal deterioration that recapitulates characteristics of PD. The administration of VCE-003.2 to these mice showed, as expected, poor activity in the different motor tests (rotarod, computer-aided actimeter) used in experimental parkinsonism, in general due to the lack of evident changes in these behaviors by LPS lesion. However, VCE-003.2, at 20 mg/kg, was highly active in improving the changes detected in LPS-lesioned mice in the cylinder rearing test. In addition, the histopathological analysis of the basal ganglia revealed a trend towards recovery at 20 mg/kg VCE-003.2 in the loss of tyrosine hydroxylase-containing nigrostriatal neurons, as well as a complete reduction in the elevated LAMP-1 immunolabeling (reflecting autophagy impairment) caused by LPS lesion. These effects were not seen at 10 mg/kg. This was associated with a partial reduction in the intense glial reactivity provoked by LPS in the substantia nigra, in particular the astroglial reactivity labeled with glial fibrillary acidic protein. The analysis using qPCR in the striatum of proinflammatory mediators, such as tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and cyclooxygenase-2, showed that the marked elevations provoked by the LPS lesion tended to be, in general, attenuated by VCE-003.2 treatment, with the greatest effects normally found with the highest dose of 20 mg/kg. In summary, our data confirm the neuroprotective potential of an oral formulation of VCE-003.2 against neuronal injury in an in vivo model of PD based on neuroinflammation, and this study opens the possibility to further the development of oral VCE-003.2 in the clinic.

Stereo-Selective Pharmacokinetics of Ilimaquinone Epimers Extracted from a Marine Sponge in Rats.

An ilimquinone (IQ) mixture isolated from Hippiospongia metachromia, consisting of IQ and epi-ilimaquinone (epi-IQ), exerts anti-HIV, anti-microbial, anti-inflammatory, and anti-cancer effects. An HPLC-MS/MS method was developed for simultaneous determination of the two epimers in rat plasma, separating them using a biphenyl column. Ascorbic acid is added during the sample preparation to ensure the stability of both isomers. The plasma concentrations of the isomers were monitored following intravenous and oral administration of the IQ mixture in rats as well as the individual epimers that were separately orally administered. Compare to IQ, epi-IQ was much more stable in rat plasma, likely due to its configurations of decalin. Both substances decayed in more than bi-exponential pattern, with an elimination rate constant of 1.2 h-1 for IQ and 1.7 h-1 for epi-IQ. The epi-IQ was distributed more widely than IQ by about two-fold. Consequently, the clearance of epi-IQ was greater than that of IQ by about three-fold. The oral absolute bioavailability for IQ was 38%, and, that for epi-IQ, was 13%. Although the systemic exposure of IQ was greater than that of epi-IQ by ~8.7-fold, the clearance of each isomer was similar when administered either orally or intravenously, when normalized for bioavailability. The stereo-specific behavior of the isomers appears to originate from differences in both their tissue distribution and gastrointestinal permeability.

HPLC-MS/MS analysis of ilimaquinone and its application in a pharmacokinetic study in rats.

Ilimaquinone, a metabolite isolated from the marine sponge Hippiospongia metachromia, has antimicrobial, cytotoxic, anti-HIV, anti-inflammatory, and anti-cancer activities. A new quantitative analytical method for determination of ilimaquinone in rat plasma using HPLC-MS/MS was developed and validated. Ascorbic acid was added to ensure the stability of ilimaquinone in plasma. After protein precipitation using acetonitrile plus diclofenac as an internal standard, the analytes were chromatographed on a biphenyl column with a mobile phase of methanol and water (8:2, v/v, including 0.1% formic acid). This method was successfully applied in a pharmacokinetic study of ilimaquinone after oral administration in rats.

Hydroxysafflor yellow A (HSYA) targets the NF-κB and MAPK pathways and ameliorates the development of osteoarthritis.

The inflammatory environment has been demonstrated to be strongly associated with the progression of osteoarthritis (OA). HSYA, the main active component in the medical and edible dual purpose plant safflower, has previously showed significant anti-inflammatory effects in several diseases. In the current study, the protective effects of HSYA in the inhibition of OA development and its underlying mechanism were examined by both in vitro and in vivo experiments. Our data indicated that interleukin-1 beta (IL-1ß) induced over-production of pro-inflammatory cytokines, such as nitric oxide (NO) and prostaglandin E2 (PGE2); also, the expression of cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) were all inhibited by pretreatment with HSYA in a dose-dependent manner (2.5 to 40 µM). Furthermore, HSYA attenuated IL-1ß-induced degradation of the extracellular matrix (ECM) by decreasing the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5). Mechanistically, HSYA suppressed IL-1ß-induced activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) cascades. Meanwhile, molecular docking studies revealed that HSYA has excellent binding abilities to p65, extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK). In addition, the protective effects of HSYA were observed in a surgically induced mouse OA model. In summary, this study provides evidence that HSYA can be applied as a potential therapeutic agent in the treatment of OA.

A theranostic nanocomposite system based on iron oxide-drug nanocages for targeted magnetic field responsive chemotherapy.

In this work, a theranostic nanocage system was developed for the targeted delivery of the anti-cancer agents camptothecin (CPT) and luotonin A (LuA). The core of the nanocage system (Fe3O4@OA-AD-SP NCs) was formed by biogenically synthesized Fe3O4 nanoparticles (NPs) decorated with a model anti-cancer drug (AD) and biosurfactant saponin (SP). The Fe3O4@OA-AD-SP NCs showed a high lipophilic AD loading efficiency (>80%) and a controlled pH-responsive drug release in stimulated cancerous cells in pH 6.4 media buffer. In addition, Fe3O4@OA-AD-SP NCs exhibited better serum protein binding efficacy at physiological pH values (7.4), furthering the important role of SP surface decoration. Particularly, these NCs showed better chemotherapeutic efficacy when examined in MCF-7 and HeLa cancer cell lines with a specific targeting capacity. Therefore, this study provides a new nano platform based on magnetic targeting and pH responsive lipophilic anticancer drug delivery to the cancer site.

Hypocrellin B-loaded, folate-conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo.

Photodynamic therapy (PDT) is considered an innovative and attractive modality to treat ovarian cancer. In the present study, a biodegradable polymer poly (ethylene glycol) (PEG)-poly (lactic acid)(PLA)-folate (FA-PEG-PLA) was prepared in order to synthesize an active-targeting, water-soluble and pharmacomodulated photosensitizer nanocarrier. Drug-loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which hypocrellin B (HB)/FA-PEG-PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (P < .05). To evaluate the targeting ability of the HB/FA-PEG-PLA micelles, a cellular uptake study in vitro was carried out, which showed significantly enhanced uptake of HB/FA-PEG-PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR-). The enhanced uptake of HB/FA-PEG-PLA micelles to cancer cells resulted in a more effective post-PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA-PEG-PLA micelles by SKOV3 cells were also observed in vivo after ip injection of folate-targeted micelles in tumor-bearing ascitic ovarian cancer animals. Drug levels in ascitic tumor tissues were increased 20-fold (P < .001), which underscored the effect of a regional therapy approach with folate targeting. Furthermore, the HB-loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results showed that our newly developed PDT photosensitizer HB/FA-PEG-PLA micelles have a high drug-loading capacity, good biocompatibility, controlled drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy.

Topical application of Hydroxysafflor Yellow A accelerates the wound healing in streptozotocin induced T1DM rats.

To investigate the effects of Hydroxysafflor Yellow A (HSYA), which is derived from safflower, on the proliferation, migration and angiogenesis of cells in vitro and its potential efficacy in vivo when topically applied to a diabetic wound. Human umbilical vein endothelial cells (HUVECs) and mouse macrophage cells (RAW264.7) were used to evaluate angiogenesis and anti-inflammatory activities, respectively. The influence of HSYA on the wound scratch assay was investigated in keratinocytes. A splinted excisional wound model in rats with TIDM induced by streptozotocin was used to assess the effects of wound healing. Collagen disposition and secretion of vascular growth factors (VEGF) as well as transforming growth factor-ß1 (TGF-ß1) were evaluated by an ELISA assay and histological staining. The in vitro results showed that HSYA could significantly enhance both the neovascularization of HUVECs and the migration of keratinocytes. It showed the significant inhibitory effect on nitric oxide production, indicating the anti-inflammatory activity of HSYA. In vivo, the topical application of HSYA significantly enhanced the wound closure rate, and the time to complete wound closure was 17 days, whereas 30 days were needed with PBS treatment. Further, treatment with HSYA exhibited significant granulation tissue formation with higher collagen content, re-epithelialization and angiogenesis according to Masson's trichrome staining evaluation, VEGE and TGF-ß1 ELISA measurement. In conclusion, HSYA application could be considered a promising therapeutic strategy for treating chronic non-healing diabetic foot ulcers.

Cell Cycle Arrest and Apoptosis Induced by Kinamycin F in Human Osteosarcoma Cells.

BACKGROUND/AIM: Kinamycin F is a bacterial metabolite which contains an unusual and potentially reactive diazo group that is known for its ability to inhibit cell growth. In this study, the potential anti-tumor activity of kinamycin F was investigated in three human osteosarcoma cell lines, MG-63, U-2 OS and HOS as an antitumor agent with a potentially novel target. MATERIALS AND METHODS: Proliferation and cell viability were measured in three human osteosarcoma cell lines by commercially available kits. We also evaluated the effects of the drug on cell cycle progression using the Muse™ Cell Analyzer. Caspase-3 activity was determined by a fluorometric EnzChek assay kit. Finally, following treatment with kinamycin F the protein levels of cyclin D3, cyclin A and cdK-2 were examined. RESULTS: Kinamycin F induced a concentration-dependent cell death in all the three cell lines. Flow cytometry revealed that kinamycin F treatment at 1 µM concentration significantly increased the cell population in the G2/M-phase (60-65%). Kinamycin F activated caspase 3 in all the three cell lines, clearly demonstrating that the growth inhibitory effect of kinamycin F can be attributed to apoptosis induction. Finally, kinamycin F suppressed osteosarcoma cell proliferation affecting cyclin A and D3 expression. CONCLUSION: Understanding the mechanism by which kinamycin F exerts its ability to inhibit cell growth may be a step forward in the development of new therapeutic strategies for the treatment of OS.

Non-benzoquinone geldanamycin analogs trigger various forms of death in human breast cancer cells.

BACKGROUND: Hsp90 proteins are important therapeutic targets for many anti-cancer drugs in clinical trials. Geldanamycin (GA) was identified as the first natural inhibitor of Hsp90, increasing evidence suggests that GA was not a good choice for clinical trials. In this study, we investigated two new non-benzoquinone geldanamycin analogs of Hsp90 inhibitors, DHQ3 and 17-demethoxy-reblastatin (17-DR), to explore the molecular mechanisms of their anti-cancer activity in vivo and vitro. METHODS: MTT and colony formation assays were used to measure cell viability. Flow cytometry, DAPI staining, ATP assay, electron microscopy, western blots, siRNAs transfection and immunofluorescence were used to determine the molecular mechanism of DHQ3- or 17-DR-induced different forms of death in human breast cancer MDA-MB-231 cells. Malachite green reagent was used to measure ATPase activity of the analogs. RESULTS: DHQ3 and 17-DR presented efficiently inhibitory effect in MDA-MB-231 cell lines, and DHQ3 induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade. And DHQ3-induced cell death was inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), but not by a caspase inhibitor z-VAD-fmk. On the other hand, 17-DR induced apoptosis in MDA-MB-231 cells, indicating a caspase-dependent killing mechanism. We further demonstrated that down-regulation of RIP1 and RIP3 by siRNA protected against DHQ3 but not 17-DR induced cell death. These results were confirmed by electron microscopy. DHQ3 and 17-DR induced the degradation of Hsp90 client proteins, and they showed strong antitumor effects in MDA-MB-231 cell-xenografted nude mice. CONCLUSIONS: These findings supported that DHQ3 and 17-DR induce different forms of death in some cancer cell line via activation of different pathways. All of the results provided evidence for its anti-tumorigentic action with low hepatotoxicity in vivo, making them promising anti-breast cancer agents.

Synergistic cardioprotective effects of Danshensu and hydroxysafflor yellow A against myocardial ischemia-reperfusion injury are mediated through the Akt/Nrf2/HO-1 pathway.

In clinical practice, the traditional Chinese medicinal herbs, Radix Salvia Miltiorrhiza and Carthamus tinctorius L., are usually prescribed in combination due to their significant cardioprotective effects. However, the mechanisms responsible for these combined effects remain unknown. Thus, in this study, we investigated the mechanisms responsible for the combined effects of Danshensu (DSS) and hydroxysafflor yellow A (HSYA) by establishing a rat model of myocardial ischemia/reperfusion (MI/R), as well as a model of hypoxia/reoxygenation (H/R) using H9c2 cells. The combination index (CI) was calculated using the median-effect method. DSS and HSYA in combination led to a CI value of <1 as regards infarct size in vivo and cell viability in vitro. The rats with MI/R injury that were treated with DSS and/or HSYA were found to have significantly lower levels of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) and malondialdehyde (MDA), and a lower expressoin of 8-hydroxydeoxyguanosine (8-OHdG), and markedly enhanced superoxide dismutase (SOD) activity. Our in vitro experiments revealed that the cells treated with DSS and/or HSYA had a reduced lactate dehydrogenase (LDH) activity and a decreased percentage of cell apoptosis (increased Bcl-2/Bax ratio, decreased expression of cleaved caspase-3). DSS and HSYA increased the expression of heme oxygenase-1 (HO-1), the phosphorylation of Akt and the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the Akt inhibitor, LY294002, partially hampered the expression of Nrf2 and HO-1. The HO-1 inhibitor, zinc protoporphyrin IX (ZnPP­IX), did not decrease the expression of p-Akt and Nrf2, although it abolished the anti-apoptotic and antioxidant effects of DSS and HSYA. The findings of our study thus demonstrate that DSS and HSYA confer synergistic cardioprotective effects through the Akt/Nrf2/HO-1 signaling pathway, to certain extent, by enhancing the antioxidant defense system and exerting anti-apoptotic effects.

A Novel 1,2-Dihydroquinoline Anticancer Agent and Its Delivery to Tumor Cells Using Cationic Liposomes.

AIM: We screened nine 1,2-dihydro-quinolines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay in HepG2 and SMMC cells and identified ethyl-2-cyano-2-(2- (methoxycarbonyl)allyl)quinoline-1(2H)-carboxylate (compound 5) as a potential anticancer agent. In order to further develop its anticancer therapeutic potential, we incorporated this agent into cationic liposomes for delivery to tumor cells. The characteristics of liposomes, their cytotoxicity and cellular uptake by tumor cells were investigated. We demonstrated that cationic 1,2-dioleoyl-3- trimethyl-ammonium-propane containing liposomes (cLips) loaded with compound 5 has superior antitumor activity compared to neutral liposomes. These data suggest cLip-compound 5 to be a promising agent that warrants further evaluation.

Hypocrellin B and paclitaxel-encapsulated hyaluronic acid-ceramide nanoparticles for targeted photodynamic therapy in lung cancer.

To increase the therapeutic efficacy of photodynamic therapy (PDT) in treating lung cancer, we developed both photosensitizer and anticancer drug encapsulated hyaluronic acid-ceramide nanoparticles. Based on our previous study, a co-delivery system of photosensitizers and anticancer agents greatly improves the therapeutic effect of PDT. Furthermore, hyaluronic acid-ceramide-based nanoparticles are ideal targeting carriers for lung cancer. In vitro phototoxicity in A549 (human lung adenocarcinoma) cells and in vivo antitumor efficacy in A549 tumor-bearing mice treated with hypocrellin B (HB)-loaded nanoparticles (HB-NPs) or hypocrellin B and paclitaxel loaded nanoparticles (HB-P-NPs) were evaluated. Cell viability assay, microscopic analysis and FACS analysis were performed for the in vitro studies and HB-P-NPs showed enhanced phototoxicity compared with HB-NPs. In the animal study, the tumor volume change and the histological analysis was studied and the anticancer efficacy improved in the order of free HB

Quinones as photosensitizer for photodynamic therapy: ROS generation, mechanism and detection methods.

Photodynamic therapy (PDT) is based on the dye-sensitized photooxidation of biological matter in the target tissue, and utilizes light activated drugs for the treatment of a wide variety of malignancies. Quinones and porphyrins moiety are available naturally and involved in the biological process. Quinone metabolites perform a variety of key functions in plants which includes pathogen protection, oxidative phosphorylation, and redox signaling. Quinones and porphyrin are biologically accessible and will not create any allergic effects. In the field of photodynamic therapy, porphyrin derivatives are widely used, because it absorb in the photodynamic therapy window region (600-900 nm). Hence, researchers synthesize drugs based on porphyrin structure. Benzoquinone and its simple polycyclic derivatives such as naphthaquinone and anthraquinones absorb at lower wavelength region (300-400 nm), which is lower than porphyrin. Hence they are not involved in PDT studies. However, higher polycyclic quinones absorb in the photodynamic therapy window region (600-900 nm), because of its conjugation and can be used as PDT agents. Redox cycling has been proposed as a possible mechanism of action for many quinone species. Quinones are involved in the photodynamic as well as enzymatic generation of reactive oxygen species (ROS). Generations of ROS may be measured by optical, phosphorescence and EPR methods. The photodynamically generated ROS are also involved in many biological events. The photo-induced DNA cleavage by quinones correlates with the ROS generating efficiencies of the quinones. In this review basic reactions involving photodynamic generation of ROS by quinones and their biological applications were discussed.

Low dose triterpene-quinone fraction from Ardisia crispa root precludes chemical-induced mouse skin tumor promotion.

BACKGROUND: Drastic increment of skin cancer incidence has driven natural product-based chemoprevention as a promising approach in anticancer drug development. Apart from its traditional usages against various ailments, Ardisia crispa (Family: Myrsinaceae) specifically its triterpene-quinone fraction (TQF) which was isolated from the root hexane extract (ACRH) was recently reported to exert antitumor promoting activity in vitro. This study aimed at determining chemopreventive effect of TQF against chemically-induced mouse skin tumorigenesis as well as elucidating its possible pathway(s). METHODS: Mice (n = 10) were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 µl) followed by, a week later, repeated promotion (twice weekly; 20 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 µl). TQF (10, 30 and 100 mg/kg) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application. Upon termination, histopathological and biochemical analysis, as well as Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and transcription factor enzyme-linked immunosorbent assay (ELISA) assays were performed to elucidate the potential mechanism of TQF. RESULTS: With comparison to the carcinogen control, results revealed that lower dose of TQF (10 mg/kg) conferred antitumor promoting effect via significant (P < 0.05) suppression against lipid peroxidation (LPO), apoptotic index (cell death) and nuclear factor-kappa B (NF-κB), along with reduction of keratinocyte proliferation; whilst its higher dose (100 mg/kg) was found to promote tumorigenesis by significantly (P < 0.05) increasing LPO and apoptotic index, in addition to aggravating keratinocyte proliferation. CONCLUSIONS: This study evidenced that TQF, particularly at its lower dosage (10 mg/kg), ameliorated DMBA/TPA-induced mouse skin tumorigenesis. Though, future investigations are warranted to determine the lowest possible therapeutic dose of TQF in subsequent in vivo chemopreventive studies.

Enhanced effect of photodynamic therapy in ovarian cancer using a nanoparticle drug delivery system.

Nanoparticles are promising novel drug delivery carriers that allow tumor targeting and controlled drug release. In the present study, we prepared poly butyl-cyanoacrylate nanoparticles (PBCA-NP) entrapped with hypocrellin B (HB) to improve the effect of photodynamic therapy (PDT) in ovarian cancer. An ovarian cancer ascites model using Fischer 344 rats and PBCA-NP entrapped with HB (HB-PBCA-NP) were formed successfully. The pharmacodynamic characteristics and biodistribution of the HB-PBCA-NP system were evaluated by comparison with HB dimethyl sulfoxide (HB-DMSO) and testing at various time-points following intraperitoneal drug administration. HB-PBCA-NP-based PDT combined with cytoreductive surgery was then administrated to the tumor-bearing animals. Kaplan-Meier survival analysis was performed to assess the therapeutic effect of the nanoparticle system. The serum HB concentration peaked 4 h after drug administration in the nanoparticle system, and 1 h with HB-DMSO. The peak exposure time of tumor tissues was also extended (4 vs. 2 h), and PBCA-NP remained present for much longer than HB-DMSO. Although PDT combined with surgery prolonged the survival time significantly compared with surgery alone (84 days, P<0.05), there was no significant difference in the survival time of animals that received either HB-PBCA-NP- or HB-DMSO-based PDT after cytoreductive surgery (99 vs. 95 days, P=0.293). PBCA-NP exhibited potential advantages in controlled drug release and tumor targeting, which was beneficial for HB-based PDT. PDT combined with surgery prolonged the survival time, suggesting that this might be an alternative treatment option for ovarian cancer.

Multicolor imaging and the anticancer effect of a bifunctional silica nanosystem based on the complex of graphene quantum dots and hypocrellin A.

An effective theranostic platform based on porous silica nanoparticles encapsulated with the complex of a photodynamic anticancer drug and graphene quantum dots (GQDs), with the bifunction of multicolor imaging and satisfactory photo-induced anticancer activity, was successfully designed and prepared for in vitro photodynamic therapy (PDT) of superficial cancer.

Hydroxysafflor yellow A ameliorates lipopolysaccharide-induced acute lung injury in mice via modulating toll-like receptor 4 signaling pathways.

Hydroxysafflor yellow A (HSYA) is a main bio-active compound important of a traditional Chinese medicine named Carthamus tinctorius L. and has been shown to possess various effects, especially anti-inflammatory benefits and potential protections against acute lung injury (ALI) in previous studies. Therefore, in this present study, we aimed to evaluating effects of HSYA on lipopolysaccharide (LPS)-induced ALI in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results demonstrated that HSYA abated LPS-induced pathological change and attenuated lung vascular permeability and edema. HSYA down-regulated both the ability of myeloperoxidase (MPO) in lung tissues and levels of inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IFN(interferon)-ß in serum. Moreover, HSYA prevented toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-ß (TRIF) protein up-expressions. In addition, the activations of mitogen-activated protein kinases including p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) were blocked by HSYA. And also, the phosphorylations of interferon regulatory factor 3 (IRF3), translocation of nuclear factor kappa B (NF-κB)/p65 and inhibitory kappa B (IκB)-α were inhibited by HSYA. In conclusion, HSYA attenuated inflammatory response in ALI mice through inhibition of TLR 4-dependent signaling pathways.

Peptide p160-coated silica nanoparticles applied in photodynamic therapy.

Peptide p160-conjugated mesoporous silica nanoparticles (MSN) were fabricated and loaded with photosensitizer hypocrellin B (HB). The results indicate that the nanocomposites have better selectivity for cancer cells and higher cytotoxicity in photodynamic therapy in vitro. The nanocomposites can be used as a novel candidate in photodynamic therapy. This may be a general and promising method to modify nanoparticles to improve their cell affinity.