Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cisplatin (CDDP) was incorporated inside single-wall carbon nanohorns with holes opened (SWNHox) by a nanoprecipitation method that involved dispersion of CDDP and SWNHox in a solvent followed by the solvent evaporation. The incorporated CDDP quantity increased from the previously reported value of 15 to 46%, and the total released quantity of CDDP also increased from 60 to 100% by changing the solvent from dimethylformamide to water. Concurrently, in vitro anticancer efficiency of CDDP@SWNHox increased to 4-6 times greater than that of the intact CDDP. In vivo, CDDP@SWNHox intratumorally injected to transplanted tumors of mice suppressed the tumor growth more than the intact CDDP. We observed that CDDP@SWNHox adhered to the cell surfaces in vitro and stayed within the tumor tissues in vivo. Therefore, we think that the CDDP released from SWNHox realized high concentrations locally at the cells in vitro and in the tissues in vivo and could efficiently attack the tumor cells. We also found that SWNHox itself had an in vivo anticancer effect, which might increase the anticancer activities of CDDP@SWNHox.
ACS Nano 2008 Oct 28
PMID:Enhancement of in vivo anticancer effects of cisplatin by incorporation inside single-wall carbon nanohorns. 1920 52

Carbon nanotube-based drug delivery holds great promise for cancer therapy. Herein we report the first targeted, in vivo killing of cancer cells using a drug-single wall carbon nanotube (SWNT) bioconjugate, and demonstrate efficacy superior to nontargeted bioconjugates. First line anticancer agent cisplatin and epidermal growth factor (EGF) were attached to SWNTs to specifically target squamous cancer, and the nontargeted control was SWNT-cisplatin without EGF. Initial in vitro imaging studies with head and neck squamous carcinoma cells (HNSCC) overexpressing EGF receptors (EGFR) using Qdot luminescence and confocal microscopy showed that SWNT-Qdot-EGF bioconjugates internalized rapidly into the cancer cells. Limited uptake occurred for control cells without EGF, and uptake was blocked by siRNA knockdown of EGFR in cancer cells, revealing the importance of EGF-EGFR binding. Three color, two-photon intravital video imaging in vivo showed that SWNT-Qdot-EGF injected into live mice was selectively taken up by HNSCC tumors, but SWNT-Qdot controls with no EGF were cleared from the tumor region in <20 min. HNSCC cells treated with SWNT-cisplatin-EGF were also killed selectively, while control systems that did not feature EGF-EGFR binding did not influence cell proliferation. Most significantly, regression of tumor growth was rapid in mice treated with targeted SWNT-cisplatin-EGF relative to nontargeted SWNT-cisplatin.
ACS Nano 2009 Feb 24
PMID:Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. 1923 65

Understanding tumor-specific metabolism under hypoxia is important to find novel targets for antitumor drug design. Here we found that tumor cells expressed higher levels of cytosolic acetyl-CoA synthetase (ACSS2) under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference (RNAi) in tumor cells enhanced tumor cell death under long-term hypoxia in vitro. Our data also demonstrated that the ACSS2 suppression slowed tumor growth in vivo. These findings showed that ACSS2 plays a significant role in tumor cell survival under hypoxia and that ACSS2 would be a potential target for tumor treatment. Furthermore, we found that tumor cells excreted acetate and the quantity increased under hypoxia: the pattern of acetate excretion followed the expression pattern of ACSS2. Additionally, the ACSS2 knockdown led to a corresponding reduction in the acetate excretion in tumor cells. These results mean that ACSS2 can conduct the reverse reaction from acetyl-CoA to acetate in tumor cells, which indicates that ACSS2 is a bi-directional enzyme in tumor cells and that ACSS2 might play a buffering role in tumor acetyl-CoA/acetate metabolism.
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PMID:Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl-CoA/acetate metabolism. 1944 15

Antiangiogenesis is an effective strategy for cancer treatment because uncontrolled tumor growth depends on tumor angiogenesis and sufficient blood supply. Great progress has been made in developing a "molecular" form of angiogenesis inhibitors; however, the narrow inhibition spectrum limits anticancer efficacy as those inhibitors that usually target a few or even a single angiogenic factor among many angiogenic factors might initially be effective but ultimately lead to the failure of the treatment due to the induction of expression of other angiogenic factors. In this work, we report that with a multiple hydroxyl groups functionalized surface, the Gd@C(82)(OH)(22) fullerenic nanoparticles (f-NPs) are capable of simultaneously downregulating more than 10 angiogenic factors in the mRNA level that is further confirmed at the protein level. After studying this antiangiogenesis activity of the f-NPs by cellular experiment, we further investigated its anticancer efficacy in vivo. A two-week treatment with the f-NPs decreased >40% tumor microvessels density and efficiently lowered the speed of blood supply to tumor tissues by approximately 40%. Efficacy of the treatment using f-NPs in nude mice was comparable to the clinic anticancer drug paclitaxel, while no pronounced side effects were found. These findings indicate that the f-NPs with multiple hydroxyl groups serve as a potent antiangiogenesis inhibitor that can simultaneously target multiple angiogenic factors. We propose that using nanoscale "particulate" itself as a new form of medicine (particulate medicine) may be superior to the traditional "molecular" form of medicine (molecular medicine) in cancer treatment.
ACS Nano 2010 May 25
PMID:Potent angiogenesis inhibition by the particulate form of fullerene derivatives. 2042 77

A series of doxorubicin-loaded polymer-caged nanobins (PCN(DXR)) were evaluated in vivo in a murine MDA-MB-231 xenograft model of triple-negative breast cancer. The cross-linked polymer cage in PCN(DXR) offers protection for the drug payload while serving as a pH-responsive trigger that enhances drug release in the acidic environments commonly seen in solid tumors and endosomes. Varying the degree of cross-linking in the polymer cage allows the surface potential of PCN(DXR), and thus the in vivo circulation lifetime of the nanocarriers, to be tuned in a facile fashion. Given these design advantages, the present study provides the first in vivo evidence that PCN(DXR) can effectively inhibit tumor growth in a murine model of breast cancer. Importantly, PCN(DXR) was well-tolerated by mice, and drug encapsulation attenuated the toxicity of free doxorubicin. Taken together, this study demonstrates the potential utility of the PCN platform in cancer therapy.
ACS Nano 2010 Sep 28
PMID:Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy. 2087 86

Stearate-g-dextran (Dex-SA) was synthesized via an esterification reaction between the carboxyl group of stearic acid (SA) and hydroxyl group of dextran (Dex). Dex-SA could self-assemble to form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC) depended on the molecular weight of Dex and the graft ratio of SA, which ranged from 0.01 to 0.08 mg mL(-1). Using doxorubicin (DOX) as a model drug, the drug encapsulation efficiency (EE%) using Dex-SA with 10 kDa molecular weight of Dex and 6.33% graft ratio of SA could reach up to 84%. In vitro DOX release from DOX-loaded Dex-SA micelles (Dex-SA/DOX) could be prolonged to 48 h, and adjusted by a different molecular weight of Dex, the graft ratio of SA, or the drug-loading content. Tumor cellular uptake test indicated that Dex-SA micelles had excellent internalization ability, which could deliver DOX into tumor cells. In vitro cytotoxicity tests demonstrated the Dex-SA/DOX micelles could maintain the cytotoxicity of commercial doxorubicin injection against drug-sensitive tumor cells. Moreover, Dex-SA/DOX micelles presented reversal activity against DOX-resistant cells. In vivo antitumor activity results showed that Dex-SA/DOX micelles treatments effectively suppressed the tumor growth and reduced the toxicity against animal body compared with commercial doxorubicin injection.
ACS Nano 2010 Nov 23
PMID:Synthesis and antitumor activity of stearate-g-dextran micelles for intracellular doxorubicin delivery. 2093 8

Stat3 is a latent transcription factor that promotes cell survival and proliferation and is often constitutively active in multiple cancers. Inhibition of Stat3 signaling pathways suppresses cell survival signals and leads to apoptosis in cancer cells, suggesting direct inhibition of Stat3 function is a viable therapeutic approach. Herein, we identify a small molecule, C48, as a selective Stat3-family member inhibitor. To determine its mechanism of action, we used site-directed mutagenesis and multiple biochemical techniques to show that C48 alkylates Cys468 in Stat3, a residue at the DNA-binding interface. We further demonstrate that C48 blocks accumulation of activated Stat3 in the nucleus in tumor cell lines that overexpress active Stat3, leading to impressive inhibition of tumor growth in mouse models. Collectively, these findings suggest Cys468 in Stat3 represents a novel site for therapeutic intervention and demonstrates the promise of alkylation as a potentially effective chemical approach for Stat3-dependent cancers.
ACS Chem Biol 2011 May 20
PMID:Alkylation of cysteine 468 in Stat3 defines a novel site for therapeutic development. 2122 22

A gold nanorod (GNR)-photosensitizer complex was developed for noninvasive near-infrared fluorescence imaging and cancer therapy. We showed that (a) fluorescence emission and singlet oxygen generation by AlPcS(4) were quenched after complex formation with GNRs; (b) 4-fold greater intracellular uptake and better in vitro phototoxicity were observed in GNR-AlPcS(4)-treated cells than in free AlPcS(4)-treated cells; and (c) after intravenous injection of the GNR-AlPcS(4) complex, tumor sites were clearly identified on near-infrared fluorescence images as early as 1 h after injection. The tumor-to-background ratio increased over time and was 3.7 at 24 h; tumor growth reduced by 79% with photodynamic therapy (PDT) alone and by 95% with dual photothermal therapy (PTT) and PDT. This novel multifunctional nanomedicine may be useful for near-infrared fluorescence imaging and PTT/PDT in various cancers.
ACS Nano 2011 Feb 22
PMID:Gold nanorod-photosensitizer complex for near-infrared fluorescence imaging and photodynamic/photothermal therapy in vivo. 2124 12

Assembly of nanoparticles as interfacial stabilizers at oil-in-water (O/W) interfaces into microscopic suprastructures for stabilizing Pickering emulsions is an intriguing focus in the fields of chemical industry and material sciences. However, it is still a major challenge to assemble nanoscale suprastructures using nanoparticles as building blocks at O/W interfaces for fabricating nanoscale emulsion droplets with applicable potential in nanomedicine. Here, we show that it is possible to fabricate the nanodroplets by assembling highly deformable nanogels into the nanoscale suprastructures at spatially confined O/W interfaces. The compressed assembly of the nanogels induced the formation of the nanoscale suprastructures upon energy input at the nanoscale O/W interface. The hydrogen bonding interaction between the nanogels at the O/W interface are possibly responsible for the stabilization of the nanoscale suprastructures. The nanoscale suprastructures are further employed to stabilize the paclitaxel-loaded nanodroplets, which are found to provide sustained release of the drug, enhanced in vitro cytotoxicity, and prolonged in vivo blood circulation. Furthermore, the tissue distribution and antitumor efficacy studies show that the nanodroplets could induce a higher drug accumulation at the tumor site and enhance tumor growth inhibition when compared with the commercial product. This approach provides a novel universal strategy to fabricate nanoscale suprastructures for stabilizing nanodroplets with built-in payloads using deformable nanoparticles and displays a promising potential in nanomedicine.
ACS Nano 2011 Apr 26
PMID:Highly compressed assembly of deformable nanogels into nanoscale suprastructures and their application in nanomedicine. 2137 20

The objective of this study is to investigate the anticancer efficacy of a drug delivery system comprised of gelatin hydrogel (jelly) containing cisplatin (CDDP)-loaded gelatin/poly(acrylic acid) nanoparticles by peritumoral implantation and to compare the treatment response between the implantation administration of the jelly and intravenous (i.v.) administration of the nanoparticles. It is found that the implantation of the jelly containing CDDP-loaded nanoparticles on tumor tissue exhibited significantly superior efficacy in impeding tumor growth and prolonging the lifetime of mice than that of i.v. injection of CDDP-loaded nanoparticles in a murine hepatoma H(22) cancer model. An in vivo biodistribution assay performed on tumor-bearing mice demonstrated that the jelly implant caused much higher concentration and retention of CDDP in tumor and lower CDDP accumulation in nontarget organs than that of i.v. injected nanoparticles. Immunohistochemical analysis demonstrated that the nanoparticles from the jelly can be distributed in tumor tissue not only by their diffusion but also by the vasculature in the implantation region into tumor interior, enabling CDDP to efficiently reach more viable cells of tumor compared with i.v. injected nanoparticles. Thus, nanoparticles for peritumoral chemotherapy are promising for higher treatment efficacy due to increased tumor-to-normal organ drug uptake ratios and improved drug penetration in tumors.
ACS Nano 2011 Apr 26
PMID:Nanospheres-incorporated implantable hydrogel as a trans-tissue drug delivery system. 2142 32


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