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1.
Adv Healthc Mater ; 12(5): e2202245, 2023 02.
Article in English | MEDLINE | ID: mdl-36373209

ABSTRACT

Up to now, chemotherapy is still the main strategy for cancer treatment. However, the emergence of chemo-resistance and systemic side effects often seriously affects the treatment and prognosis. Herein, an intelligent nanoplatform based on dendritic mesoporous organosilica nanoparticles (DMON) is constructed. The encapsulated phase-change material, 1-tetradecanol (TD) can serve as a "doorkeeper" and enable the responsive release of drugs based on the temperature changes. Meanwhile, polyethylene glycol (PEG) is used to improve the dispersibility and biocompatibility. Cisplatin is chosen as the model of chemotherapy drug, which is co-loaded with indocyanine green (ICG) in DMON to produce DMON-PEG-cisplatin/ICG-TD (DPCIT). Exciting, the hyperthermia and reactive oxygen species induced by ICG under the NIR-laser irradiation will initiate a phase transition of TD to release cisplatin, thus leading a combined therapy (chemo/photothermal/photodynamic therapy). The results indicated that under laser irradiation, DPCIT can kill cancer cells and inhibit tumor growth efficiently. In addition, the designed nanoplatform reveals minimal systemic toxicity in vivo, in contrast, the distinct liver damage can be observed by the direct treatment of cisplatin. Overall, this research may provide a general approach for the targeted delivery and controlled release of chemotherapy drugs to realize a cooperatively enhanced multimodal tumor therapy.


Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Photochemotherapy , Humans , Phototherapy/methods , Cisplatin/pharmacology , Polyethylene Glycols , Indocyanine Green/pharmacology , Neoplasms/drug therapy , Doxorubicin/pharmacology , Cell Line, Tumor
2.
Food Chem ; 401: 134117, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36096001

ABSTRACT

Although nanocomposite films had shown excellent potential in antibacterial food packaging, their potential harmful impact limits their further application in reality. Therefore, exploring a Generally Recognized As Safe (GRAS) nanomaterial that has antibacterial ability is the pioneer for the fabrication of a real edible nanocomposite-based antibacterial packaging film. Herein, for the first time by using the natural nanostructure extracted from cuttlefish ink, an edible antibacterial food packaging with high safety were constructed. The natural melanin nanoparticles (NMPs) in cuttlefish ink have good photothermal conversion ability. As such, by incorporating with natural pectin (PC) film and with near infrared (NIR) irradiation triggering, the results show that PC/NMPs films perform high-efficiency and short-term bactericidal activity against foodborne pathogenic bacteria, including thermotolerant Listeria monocytogenes. The sterilization rate could reach more than 90 % within only 5 min. Also, this nanocomposite film showed better mechanical properties, thermal stability and barrier properties than the neat pectin film. Antibacterial test on food sample also proved the good antibacterial ability of the PC/NMPs films. Therefore, exploring GRAS natural functional nanocomposite film is expected to be the effective way to promote edible nano-antibacterial packaging.


Subject(s)
Edible Films , Nanoparticles , Food Packaging/methods , Melanins , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Pectins/pharmacology , Pectins/chemistry
3.
ACS Appl Mater Interfaces ; 14(32): 36503-36514, 2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35925873

ABSTRACT

Ovarian cancer has become an urgent threat to global female healthcare. Cisplatin, as the traditional chemotherapeutic agent against ovarian cancer, retains several limitations, such as drug resistance and dose-limiting toxicity. In order to solve the above problems and promote the therapeutic effect of chemotherapy, combining chemotherapy and phototherapy has aroused wide interest. In this study, we constructed a versatile cisplatin prodrug-conjugated therapeutic platform based on ultrasmall CuS-modified Fe(III)-metal-organic frameworks (MIL-88) (named M-Pt/PEG-CuS) for tumor-specific enhanced synergistic chemo-/phototherapy. After intravenous injection, M-Pt/PEG-CuS presented obvious accumulation in tumor and Fe(III)-MOFs possessed magnetic resonance imaging (MRI) to guide synergy therapy. Both in vitro and in vivo experimental results showed that M-Pt/PEG-CuS could not only successfully inhibit tumor growth by combining chemotherapy and NIR-II PTT but also avoid the generation of liver damage by the direct treatment of cisplatin(II). Our work presented the development of the nanoplatform as a novel NIR-II photothermal agent, as well as gave a unique combined chemo-photothermal therapy strategy, which might provide new ways of ovarian cancer therapy for clinical translation.


Subject(s)
Nanoparticles , Ovarian Neoplasms , Prodrugs , Cisplatin/pharmacology , Cisplatin/therapeutic use , Doxorubicin/pharmacology , Female , Ferric Compounds , Humans , Magnetic Resonance Imaging , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/drug therapy , Phototherapy , Photothermal Therapy , Prodrugs/pharmacology
4.
Acta Biomater ; 148: 218-229, 2022 08.
Article in English | MEDLINE | ID: mdl-35705171

ABSTRACT

Triple negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC usually have poor prognosis. Hence, it is urgent to develop new comprehensive treatments for TNBC. The combination of heat shock protein (HSP) inhibitor and the photothermal agent can reduce the temperature required to kill tumor cells, thus achieving mild-temperature photothermal therapy (PTT). Compared with traditional PTT, mild-temperature PTT not only decreases tumor thermoresistance introduced by the overexpression of HSP, but also reduces the damage to normal tissues. Meanwhile, Azo initiator 2,2-azobis[2-(2-imidazolin-2-yl) propane]-dihydroch-loride (AIPH) can be thermally decomposed to generate oxygen-independent free radicals. Herein, a new therapeutic multifunctional nanoplatform (M-17AAG-AIPH) by loading heat shock protein 90 (HSP90) inhibitor (17AAG) and AIPH incorporated into mesoporous polydopamine (MPDA) was successfully constructed for mild-temperature PTT combined with oxygen-independent cytotoxic free radicals against TNBC. Under 808 nm laser irradiation, the mild-temperature PTT arising from the combined effects of 17AAG and MPDA induced a rapid release and decomposition of AIPH, promoting the apoptosis of cancer cells in hypoxic microenvironments. Both in vitro and in vivo results showed that the designed nanoplatform can significantly inhibit tumor growth and provided an efficient new therapeutic strategy for TNBC. STATEMENT OF SIGNIFICANCE: There is still an urgent need for new strategies for the treatment of triple negative breast cancer (TNBC). In this work, we successfully constructed a new therapeutic multifunctional nanoplatform (M-17AAG-AIPH) by co-carrying heat shock protein 90 (HSP90) inhibitor (17AAG) and AIPH on mesoporous polydopamine (MPDA). MPDA owned good biocompatibility and outstanding photothermal-conversion ability. The loading of 17AAG can reduce the heat resistance of tumor cells via specifically inhibiting the activity of HSP90, so as to achieve mild-temperature PTT. Meanwhile, 17AAG and MPDA mediated mild-temperature PTT promoted the decomposition of AIPH into oxygen-independent cytotoxic free radicals. Both in vitro and in vivo results showed that M-17AAG-AIPH can significantly inhibit tumor growth and provided an efficient new therapeutic strategy for TNBC.


Subject(s)
Antineoplastic Agents , Hyperthermia, Induced , Nanoparticles , Triple Negative Breast Neoplasms , Cell Line, Tumor , Free Radicals , Heat-Shock Proteins , Humans , Hyperthermia, Induced/methods , Nanoparticles/chemistry , Oxygen , Phototherapy/methods , Photothermal Therapy , Temperature , Triple Negative Breast Neoplasms/therapy , Tumor Microenvironment
5.
J Nanobiotechnology ; 20(1): 187, 2022 Apr 12.
Article in English | MEDLINE | ID: mdl-35413842

ABSTRACT

BACKGROUND: Non-redundant properties such as hypoxia and acidosis promote tumor metabolic adaptation and limit anti-cancer therapies. The key to the adaptation of tumor cells to hypoxia is the transcriptional and stable expression of hypoxia-inducible factor-1 alpha (HIF-1α). The phosphorylation-activated tumorigenic signal PI3K/AKT/mTOR advances the production of downstream HIF-1α to adapt to tumor hypoxia. Studies have elucidated that acid favors inhibition of mTOR signal. Nonetheless, carbonic anhydrase IX (CAIX), overexpressed on membranes of hypoxia tumor cells with pH-regulatory effects, attenuates intracellular acidity, which is unfavorable for mTOR inhibition. Herein, a drug delivery nanoplatform equipped with dual PI3K/mTOR inhibitor Dactolisib (NVP-BEZ235, BEZ235) and CAIX inhibitor 4-(2-aminoethyl) benzene sulfonamide (ABS) was designed to mitigate hypoxic adaptation and improve breast cancer treatment. RESULTS: ABS and PEG-NH2 were successfully modified on the surface of hollow polydopamine (HPDA), while BEZ235 and Chlorin e6 (Ce6) were effectively loaded with the interior of HPDA to form HPDA-ABS/PEG-BEZ235/Ce6 (H-APBC) nanoparticles. The release of BEZ235 from H-APBC in acid microenvironment could mitigate PI3K/mTOR signal and resist HIF-1α-dependent tumor hypoxia adaptation. More importantly, ABS modified on the surface of H-APBC could augment intracellular acids and enhances the mTOR inhibition. The nanoplatform combined with phototherapy inhibited orthotopic breast cancer growth while reducing spontaneous lung metastasis, angiogenesis, based on altering the microenvironment adapted to hypoxia and extracellular acidosis. CONCLUSION: Taken together, compared with free BEZ235 and ABS, the nanoplatform exhibited remarkable anti-tumor efficiency, reduced hypoxia adaptation, mitigated off-tumor toxicity of BEZ235 and solved the limited bioavailability of BEZ235 caused by weak solubility.


Subject(s)
Breast Neoplasms , Carbonic Anhydrase IX , Nanoparticles , Phototherapy , Quinolines , TOR Serine-Threonine Kinases , Acidosis , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carbonic Anhydrase IX/antagonists & inhibitors , Cell Hypoxia , Cell Line, Tumor , Cell Proliferation , Drug Delivery Systems , Humans , Imidazoles , Molecular Targeted Therapy , Nanoparticles/administration & dosage , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Quinolines/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism , Tumor Hypoxia
6.
Front Cell Dev Biol ; 10: 827940, 2022.
Article in English | MEDLINE | ID: mdl-35252193

ABSTRACT

In the male reproductive tract, the epididymis is an essential organ for sperm maturation, in which sperm cells acquire mobility and the ability to fertilize oocytes while being stored in a protective microenvironment. Epididymal function involves a specialized luminal microenvironment established by the epithelial cells of epididymal mucosa. Low-calcium concentration is a unique feature of this epididymal luminal microenvironment, its relevance and regulation are, however, incompletely understood. In the rat epididymis, the vitamin D-related calcium-dependent TRPV6-TMEM16A channel-coupler has been shown to be involved in fluid transport, and, in a spatially complementary manner, vitamin K2-related γ-glutamyl carboxylase (GGCX)-dependent carboxylation of matrix Gla protein (MGP) plays an essential role in promoting calcium-dependent protein aggregation. An SNP in the human GGCX gene has been associated with asthenozoospermia. In addition, bioinformatic analysis also suggests the involvement of a vitamin B6-axis in calcium-dependent MGP-mediated protein aggregation. These findings suggest that vitamins interact with calcium homeostasis in the epididymis to ensure proper sperm maturation and male fertility. This review article discusses the regulation mechanisms of calcium homeostasis in the epididymis, and the potential role of vitamin interactions on epididymal calcium homeostasis, especially the role of matrix calcium in the epididymal lumen as a cofactor for the carboxylated MGP-mediated scavenging function.

7.
J Nanobiotechnology ; 19(1): 261, 2021 Sep 04.
Article in English | MEDLINE | ID: mdl-34481495

ABSTRACT

BACKGROUND: Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (·OH) to kill cancer cells, holds great promise in tumor therapy due to its high selectivity. However, the therapeutic effect is significantly limited by insufficient intracellular H2O2 level in tumor cells. Fortunately, ß-Lapachone (Lapa) that can exert H2O2-supplementing functionality under the catalysis of nicotinamide adenine dinucleotide (phosphate) NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme offers a new idea to solve this problem. However, extensive DNA damage caused by high levels of reactive oxygen species can trigger the "hyperactivation" of poly(ADP-ribose) polymerase (PARP), which results in the severe interruption of H2O2 supply and further the reduced efficacy of CDT. Herein, we report a self-amplified nanocatalytic system (ZIF67/Ola/Lapa) to co-deliver the PARP inhibitor Olaparib (Ola) and NQO1-bioactivatable drug Lapa for sustainable H2O2 production and augmented CDT ("1 + 1 + 1 > 3"). RESULTS: The effective inhibition of PARP by Ola can synergize Lapa to enhance H2O2 formation due to the continuous NQO1 redox cycling. In turn, the high levels of H2O2 further react with Co2+ to produce the highly toxic ·OH by Fenton-like reaction, dramatically improving CDT. Both in vitro and in vivo studies demonstrate the excellent antitumor activity of ZIF67/Ola/Lapa in NQO1 overexpressed MDA-MB-231 tumor cells. Importantly, the nanocomposite presents minimal systemic toxicity in normal tissues due to the low NQO1 expression. CONCLUSIONS: This design of nanocatalytic system offers a new paradigm for combing PARP inhibitor, NQO1-bioactivatable drug and Fenton-reagents to obtain sustained H2O2 generation for tumor-specific self-amplified CDT.


Subject(s)
Antineoplastic Agents/pharmacology , Nanostructures/chemistry , Nanostructures/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Animals , Apoptosis , Cell Line, Tumor , DNA Damage/drug effects , Humans , Hydrogen Peroxide/metabolism , Mice , NAD(P)H Dehydrogenase (Quinone) , Nanoparticles , Naphthoquinones , Poly (ADP-Ribose) Polymerase-1 , Reactive Oxygen Species/metabolism
8.
Hum Gene Ther ; 32(15-16): 828-838, 2021 08.
Article in English | MEDLINE | ID: mdl-33339472

ABSTRACT

Ovarian cancer is the most lethal gynecological cancer, most patients relapse within 12-24 months, and eventually die, especially platinum-resistant patients. Gene therapy has been one of the most potential methods for tumor treatment. Bone marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. Sodium iodide symporter (NIS) is an intrinsic membrane glycoprotein and can concentrate 131I, which is important for radionuclide therapy and nuclear medicine imaging in recent years. However, the rapid iodine efflux has become a bottleneck for NIS-mediated radionuclide gene therapy. Our previous studies found that the early growth response-1 (Egr1) promoter containing CC(A/T)6GG (CArG) elements had an 131I radiation-positive feedback effect on the NIS gene. Other research showed the synthesized Egr1 promoter containing four CArG elements, E4, was nearly three times as sensitive as the Egr1 promoter. In our study, BMSC-E4-NIS was engineered to express NIS under the control of E4 promoter using lentivirial vectors. After BMSC-E4-NIS implantation, no tumors were seen in BALB/c nude mice and BMSC-E4-NIS did not promote the growth of SKOV3 tumor. BMSCs migrated toward ovarian cancer samples in chemotaxis assays and to ovarian tumors in mice. Using micro-single-photon emission computed tomography/computed tomography (SPECT/CT) imaging, we found that E4 promoter produced a notable increase in 125I uptake after 131I irradiation, the radionuclide uptake is almost three and six times more than Egr1 and cytomegalovirus (CMV) promoters. These studies confirmed the feasibility of using BMSCs as carriers for lentivirus-mediated E4-NIS gene therapy for ovarian cancer. Further research on BMSC-E4-NIS gene therapy for ovarian cancer in vivo will also be carried on, and if successful, this might provide a new adjuvant therapeutical option for platinum-resistant ovarian cancer patients and provide a new method for dynamic evaluation of curative effect.


Subject(s)
Mesenchymal Stem Cells , Ovarian Neoplasms , Symporters , Animals , Cell Line, Tumor , Feasibility Studies , Female , Humans , Mice , Mice, Nude , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Symporters/genetics
9.
Food Chem ; 338: 127749, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-32805690

ABSTRACT

Lycium barbarum L. polysaccharides (LBPs) with outstanding biological activities are of increasing interest. Traditional purification approaches are time-consuming and often involve toxic solvents that destroy the functionality and structure of polysaccharides. Herein, we report a sustainable and nondestructive strategy for purifying LBPs using graphene-based nano-decoloration. The amination of graphene oxide (GO) enables the resulted aminated reduced GO (NH2-rGO) with abundant sp2-hybridized carbon domains, displaying high adsorption capacity toward pigments in crude polysaccharides. As such, within 5 min, NH2-rGO can highly effectively and fast to decolor LBPs, with a high decoloration ratio of 98.72% and a high polysaccharides retention ratio of 95.62%. Importantly, compared with traditional decoloration methods, NH2-rGO is nondestructive toward LBPs and has good reusability. Moreover, it exhibited widespread-use decoloration performance to decolor several common plant species. Overall, our proposed nano-decoloration approach is a general-purpose, sustainable, and nondestructive method to purify LBPs.


Subject(s)
Drugs, Chinese Herbal/chemistry , Graphite/chemistry , Lycium/chemistry , Color , Nanostructures/chemistry
10.
Nanoscale ; 12(41): 21234-21247, 2020 Oct 29.
Article in English | MEDLINE | ID: mdl-33063070

ABSTRACT

A combination of chemotherapy and phototherapy has been proposed as a promising treatment for esophageal cancer (EC). Irinotecan as a first-line treatment option is widely prescribed for metastatic EC, however, its clinical application is extremely restricted by the low conversion rate to SN38, severe myelosuppression and diarrhea. As a more potent active metabolite of irinotecan, SN38 is a better substitution for irinotecan, but the poor water solubility and the difficulty of encapsulation hindered its medical application. Herein, a multifunctional SN38-conjugated nanosystem (FA-PDA@PZM/SN38@BSA-MnO2, denoted as FA-PPSM) is designed for overcoming the above-mentioned drawbacks and achieving collaborative chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT). The tumor acidic microenvironment induces decomposition of BSA-MnO2 nanoparticles into O2 and Mn2+, thus enhancing oxygen-dependent PDT efficacy; meanwhile, Mn2+ can be employed as a magnetic resonance imaging (MRI) contrast agent. Under 650 and 808 nm laser irradiation, the FA-PPSM nanocomposites exhibit superior antitumor efficacy in Eca-109-tumor bearing mice. Notably, there is low gastrointestinal toxicity and myelosuppression in the FA-PPSM treated mice compared with those treated with irinotecan (alone). Taken together, this work highlights the great potential of the FA-PPSM nanocomposites for MRI-guided chemotherapy in combination with endoscopic light therapy for esophageal cancer.


Subject(s)
Esophageal Neoplasms , Nanoparticles , Animals , Cell Line, Tumor , Diarrhea , Esophageal Neoplasms/drug therapy , Irinotecan , Manganese Compounds , Mice , Oxides , Phototherapy , Tumor Microenvironment
11.
Nanoscale ; 12(37): 19149-19158, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32936174

ABSTRACT

The rampant usage of antibiotics has led to the emergence of toxicity, especially hepatotoxicity and the emergence of microbial drug resistance. Hence, a series of novel hepatoprotective, biocompatible, antibacterial silver nanoformulations (AS-AgNPs) were developed by using the important Chinese medicinal plant Angelica sinensis. The different size of AS-AgNPs were characterized by UV-Visible spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The size-dependent antibacterial properties of AS-AgNPs were investigated against Gram-positive, Gram-negative and multi-drug resistant bacteria. The minimum inhibitory concentration (MIC) of AS-AgNPs with different size against six bacteria was found to be in the range of 5-100 µg mL-1 with no resistance till 12 cycles. TEM and SEM results of bacteria after the treatment suggested that AS-AgNPs disrupted the cell membrane by creating pores. The cytocompatibility and cytoprotective effect of AS-AgNPs were evaluated against HepG2 cell lines, which showed that 85% of cells were viable up to 100 µg mL-1 of the concentration with almost no change in AST and ALT levels. Further, a logic combinatorial library, including basic logic gates (AND, OR, NOR, INHIBIT, IMPLICATION, and YES), three input logic gates (OR, and NOR) and combinatorial gates (INH-OR, INH-YES, INH-INH, AND-NOR, and NOT-AND-NOR) were designed by integrating multi-components based on the interaction between AS-AgNP1 and bacteria, where DiSC3(5) was used as the signal reporter. This system clearly demonstrates the ability of simple logic circuits to perform sophisticated analysis for the detection of multiple bacteria.


Subject(s)
Angelica sinensis , Metal Nanoparticles , Anti-Bacterial Agents/pharmacology , Bacteria , Microbial Sensitivity Tests , Plant Extracts/pharmacology , Silver , Spectroscopy, Fourier Transform Infrared
12.
Commun Biol ; 3(1): 343, 2020 07 03.
Article in English | MEDLINE | ID: mdl-32620811

ABSTRACT

Despite its great potential in cancer therapy, phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), often cause metastasis of tumors. Immunotherapy has revolutionized the cancer treatment owing to the capability of activating immune system to eliminate tumors. However, the integration of phototherapy and immunotherapy in a single nanoagent for cancer therapy is still a challenging task. Here, we fabricated (Cu9S5@mSiO2-PpIX@MnO2@CpG (CSPM@CpG)) as a synergistic therapeutic model for phototherapy enhanced immunotherapy. The intracellular uptake of cytosine-phosphate-guanine (CpG) promoted the infiltration of cytotoxic T lymphocytes (CTLs) in tumor tissue, further stimulating the production of interferon gamma (IFN-γ) and remarkably elevating the immune response level. Excellent anti-tumor effects have been achieved by synergistic PTT/PDT/immunotherapy. The metastasis of tumors was effectively inhibited by the immune response of CpG. Thus, our proposed work provides a strategy to combine phototherapy with immunotherapy to enhance the therapeutic efficiency and further inhibit metastasis of tumors.


Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Copper/chemistry , Drug Delivery Systems , Hot Temperature , Metal Nanoparticles/administration & dosage , Photochemotherapy/methods , Animals , Antineoplastic Agents/chemistry , Apoptosis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Proliferation , Cytosine/chemistry , Drug Liberation , Female , Guanine/chemistry , Humans , Immunotherapy , Metal Nanoparticles/chemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Oxides/chemistry , Phosphates/chemistry , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
13.
Medicine (Baltimore) ; 99(16): e19720, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32311960

ABSTRACT

BACKGROUND: Hemorrhoidal disease (HD) is one of the commonest proctologic condition in the general population. Medical therapy for HD has not been formally confirmed due to the inconsistent of results. Liang-Xue-Di-Huang Decoction, a kind of ancient Chinese classical prescription, has been used to treat HD from the 19th century in China. However, clinical research of Liang-Xue-Di-Huang Decoction in the treatment of HD was lack. We designed this study to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction in the treatment of HD. METHODS/DESIGN: A randomized, controlled, double blind, double-mimetic agent, and multicenter trial to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction is proposed. HD patients (stage I, II, III) will be randomly assigned into experimental group or control group. HD patients will receive a 7-day treatments and a 7-day follow-up. The primary outcome measure is the Hemorrhoid Bleeding Score in 7 and 14 days. The Secondary outcome measures are Goligher prolapse score and quality-of-life score in 7 and 14 days. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction in treatment of HD.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Hemorrhage/drug therapy , Hemorrhoids/drug therapy , Hemorrhage/etiology , Hemorrhoids/complications , Humans , Medicine, Chinese Traditional , Phytotherapy
14.
J Mater Chem B ; 8(5): 935-944, 2020 02 07.
Article in English | MEDLINE | ID: mdl-31912837

ABSTRACT

Multifunctional nanotheranostic systems with both therapeutic and imaging functions are highly desired for the development of more effective and less toxic anti-tumor drugs. Herein, a simple but effective method is reported to fabricate a novel PCN-CuS-FA-ICG-based nanoplatform for dual-modal imaging-guided synergistic photothermal/photodynamic therapy. Porphyrinic metal-organic frameworks with CuS NPs are obtained in aqueous solution via a simple post-synthesis strategy. Furthermore, to obtain a more effective therapy, indocyanine green (ICG) was incorporated into the multifunctional theranostic platform to promote the photothermal therapeutic effect. The as-prepared PCN-CuS-FA-ICG not only exhibits an excellent 1O2 generation efficiency under 650 nm irradiation to achieve remarkable photodynamic cell killing, but also presents outstanding photothermal conversion under 808 nm irradiation to destroy tumor tissues by hyperthermia. In particular, the nanotherapeutic agent realized fluorescence and thermal imaging dual-modal imaging-guided cancer treatment. Meanwhile, in vivo experiments confirmed the evident accumulation of nanoparticles (NPs) at local tumors, and tumor growth was inhibited obviously via synergistic photothermal/photodynamic therapy with negligible side effects.


Subject(s)
Antineoplastic Agents/pharmacology , Coloring Agents/pharmacology , Hyperthermia, Induced , Metal-Organic Frameworks/pharmacology , Nanoparticles/chemistry , Photochemotherapy , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Coloring Agents/chemical synthesis , Coloring Agents/chemistry , Copper/chemistry , Copper/pharmacology , Drug Screening Assays, Antitumor , Humans , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Infrared Rays , Materials Testing , Metal-Organic Frameworks/chemical synthesis , Metal-Organic Frameworks/chemistry , Optical Imaging , Particle Size , Singlet Oxygen/analysis , Singlet Oxygen/metabolism , Surface Properties , Tumor Cells, Cultured
15.
Adv Mater ; 31(52): e1904997, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31721331

ABSTRACT

Cancer immunotherapy has achieved promising clinical responses in recent years owing to the potential of controlling metastatic disease. However, there is a limited research to prove the superior therapeutic efficacy of immunotherapy on breast cancer compared with melanoma and non-small-cell lung cancer because of its limited expression of PD-L1, low infiltration of cytotoxic T lymphocytes (CTLs), and high level of myeloid-derived suppressor cells (MDSCs). Herein, a multifunctional nanoplatform (FA-CuS/DTX@PEI-PpIX-CpG nanocomposites, denoted as FA-CD@PP-CpG) for synergistic phototherapy (photodynamic therapy (PDT), photothermal therapy (PTT) included) and docetaxel (DTX)-enhanced immunotherapy is successfully developed. The nanocomposites exhibit excellent PDT efficacy and photothermal conversion capability under 650 and 808 nm irradiation, respectively. More significantly, FA-CD@PP-CpG with no obvious side effects can remarkably inhibit the tumor growth in vivo based on a 4T1-tumor-bearing mice modal. A low dosage of loaded DTX in FA-CD@PP-CpG can promote infiltration of CTLs to improve efficacy of anti-PD-L1 antibody (aPD-L1), suppress MDSCs, and effectively polarize MDSCs toward M1 phenotype to reduce tumor burden, further to enhance the antitumor efficacy. Taken together, FA-CD@PP-CpG nanocomposites offer an efficient synergistic therapeutic modality in docetaxel-enhanced immunotherapy for clinical application of breast cancer.


Subject(s)
Docetaxel/chemistry , Oligonucleotides/chemistry , T-Lymphocytes, Cytotoxic/immunology , Animals , Antibodies, Monoclonal, Humanized/chemistry , Antibodies, Monoclonal, Humanized/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Copper/chemistry , Docetaxel/pharmacology , Docetaxel/therapeutic use , Drug Carriers/chemistry , Folic Acid/chemistry , Humans , Immunotherapy , Lasers , Mice , Nanocomposites/chemistry , Phototherapy , Polyethyleneimine/chemistry , Protoporphyrins/chemistry , Reactive Oxygen Species/metabolism , T-Lymphocytes, Cytotoxic/cytology , T-Lymphocytes, Cytotoxic/metabolism , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/therapy
16.
Carbohydr Polym ; 226: 115283, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31582088

ABSTRACT

Deproteinization is a crucial step for the purification of polysaccharides from natural biomass. However, traditional deproteinization technologies often suffer from complicated operating processes and the usage of toxic chemical reagents. Herein, an advanced and universal deproteinization method based on dual-functional adsorbent consisted of preferential protein adsorption coating of tannic acid-FeIII (TA-FeIII) and magnetic Fe3O4 (Fe3O4@TA-FeIII, abbreviated as FTF NPs) was developed. The proposed FTF NPs showed remarkable efficiency to remove protein from Lycium barbarum L. polysaccharides (LBPs) with deproteinization ratio of 96%, higher than the typical Sevag method (85%). Detailed adsorption kinetics studies demonstrated deproteinization process reached equilibrium after 10 min, faster than other reported deproteinization adsorbents. Furthermore, FTF NPs are structurally and functionally nondestructive as regards LBPs without using organic reagents. Also, it exhibited widespread-use deproteinization performance to several common plant species. Therefore, the proposed nano-separation based on TA-FeIII complex is an advanced and universal tool to high-efficiently deproteinize plant polysaccharides.


Subject(s)
Drugs, Chinese Herbal/isolation & purification , Ferric Compounds/chemistry , Polysaccharides/isolation & purification , Tannins/chemistry , Adsorption , Kinetics , Lycium/metabolism , Magnetic Phenomena
17.
Chem Commun (Camb) ; 54(98): 13841-13844, 2018 Dec 06.
Article in English | MEDLINE | ID: mdl-30468218

ABSTRACT

A novel, simple, one-step and one-tube detection method was developed for ultrasensitive detection of polynucleotide kinase (PNK) activity on the basis of dual enzyme-synergistic signal amplification. This method was also demonstrated to work well for PNK inhibitor screening and endogenous PNK detection in cell lysates at a single-cell level.


Subject(s)
Enzyme Assays/methods , Polynucleotide 5'-Hydroxyl-Kinase/analysis , Drug Evaluation, Preclinical/economics , Drug Evaluation, Preclinical/methods , Enzyme Assays/economics , HeLa Cells , Humans , Polynucleotide 5'-Hydroxyl-Kinase/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Spectrometry, Fluorescence/methods , Temperature
18.
ACS Nano ; 10(2): 2766-73, 2016 Feb 23.
Article in English | MEDLINE | ID: mdl-26794807

ABSTRACT

Upconversion (UC) luminescent lanthanide nanoparticles (LNPs) are expected to play an important role in imaging and photodynamic therapy (PDT) in vitro and in vivo. However, with the absorption of UC emissions by photosensitizers (PSs) to generate singlet oxygen ((1)O2) for PDT, the imaging signals from LNPs are significantly weakened. It is important to activate another imaging route to track the location of the LNPs during PDT process. In this work, Nd(3+)-sensitized LNPs with dual-band visible and near-infrared (NIR) emissions under single 808 nm excitation were reported to address this issue. The UC emissions in green could trigger covalently linked rose bengal (RB) molecules for efficient PDT, and NIR emissions deriving from Yb(3+) and magnetic resonance imaging (MRI) were used for imaging simultaneously. Notably, the designed therapeutic platform could further effectively avoid the overheating effect induced by the laser irradiation, due to the minimized absorption of biological media at around 808 nm. TdT-mediated dUTP nick end labeling (TUNEL) assay showed serious cell apoptosis in the tumor after PDT for 2 weeks, leading to an effective tumor inhibition rate of 67%. Benefit from the PDT, the tumor growth-induced liver and spleen burdens were largely attenuated, and the liver injury was also alleviated. More importantly, pulmonary and hepatic tumor metastases were significantly reduced after PDT. The Nd(3+)-sensitized LNPs provide a multifunctional nanoplatform for NIR light-assisted PDT with minimized heating effect and an effective inhibition of tumor growth and metastasis.


Subject(s)
Lanthanoid Series Elements/chemistry , Luminescence , Metal Nanoparticles/chemistry , Neoplasms, Experimental/diagnostic imaging , Photochemotherapy/methods , Animals , Apoptosis , HeLa Cells , Humans , Magnetic Resonance Imaging , Mice , Mice, Inbred BALB C , Neoplasm Metastasis , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Photosensitizing Agents/chemistry , Rose Bengal/chemistry
19.
Biosens Bioelectron ; 79: 205-12, 2016 May 15.
Article in English | MEDLINE | ID: mdl-26706942

ABSTRACT

We report here an ultrasensitive strategy based on the recognition-induced conformational alteration of aptamer and fluorescence turn-on abilities of guanine-rich (G-rich) DNA sequence in proximity to silver nanoclusters for adenosine triphosphate (ATP), adenosine (A) and thrombin (TB) detection. Herein, we designed two tailored DNA sequences noted as complementary DNA (abbreviated as c-DNA) and signal probe DNA (abbreviated as s-DNA), respectively. c-DNA is designed as a special structure consisting of a sequence complementary to aptamer at the 3'-end and a guanine-rich DNA sequence at the 5'-end; s-DNA contains a cytosine-rich sequence responsible for Ag NCs templated synthesis at the 3'-end and a link sequence (part of aptamer) complementary to partial of the c-DNA at the 5'-end. In the presence of target, the aptamer associated with the target, resulting in the formation of duplex DNA (dsDNA), the DNA-Ag NCs thereafter could close to the guanine-rich sequence, leading to enhanced fluorescence signal readout. The widespread application of the sensing system is achieved success in the detection of three biomolecules. ATP, adenosine and thrombin in the range of 0.5-8.0 µM, 0.5-7.0 µM and 50-900 nM could be linearly detected with the detection limits of 91.6 nM, 103.4 nM and 8.4 nM, respectively. This label-free and turn-on fluorescent sensing system employing the mechanism proposed here turns out to be sensitive, selective, and convenient for the detection of biomolecules without washing and separation steps.


Subject(s)
Adenosine Triphosphate/isolation & purification , Adenosine/isolation & purification , Biosensing Techniques , Thrombin/isolation & purification , Aptamers, Nucleotide/chemistry , Fluorescence , Light , Metal Nanoparticles/chemistry , Silver/chemistry
20.
Huan Jing Ke Xue ; 32(3): 870-4, 2011 Mar.
Article in Chinese | MEDLINE | ID: mdl-21634190

ABSTRACT

Toxicity analysis was studied from using seed germination as an ecological indicator, and the earthworm was considered as a suitable biomonitor animal to determine the ecological hazard of polluted soil. The main results are as follows: These crop seeds have significantly different responses to petroleum pollution. Compared with those plants in clean soil, the germination of most crop seeds planted in contaminated soils is obviously inhabited. Soybean, horse bean and maize are the crop affected most adversely. Fortunately, strong endurance is observed for green soybean under 4 different levels of petroleum pollution, and the seed germination rate are all above 90%. When exposed to pollutants, earthworms could be changed obviously on the level of physiology. That might affect the survival and growth capacity of earthworms, and changed population finally. In high petroleum contaminated soil (concentration of petroleum > 30 000 mg/kg) earthworms can only survive about 5 days. The results suggest that petroleum pollution has great poison to earthworms and can kill earthworms finally. Because pollutants make them dehydrate. Even on the low pollution level, the survival time of earthworm is still very short (3 d or so) in the treated petroleum-contaminated soil. Because after a petroleum ether-treated, the nutrients of soil are disposed with the oil, and the organic matter and other nutrients of the soil have a great impact on the survival of earthworms.


Subject(s)
Environmental Restoration and Remediation/methods , Hydrocarbons/toxicity , Petroleum/toxicity , Plants/drug effects , Soil Pollutants/toxicity , Animals , Chemical Phenomena , Germination , Hydrocarbons/isolation & purification , Oligochaeta/drug effects , Petroleum/analysis , Plant Development , Soil Pollutants/isolation & purification
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