The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform

Zhengrong Cui - One of the best experts on this subject based on the ideXlab platform.

  • The effect of the Acid-sensitivity of 4-(N)-stearoyl gemcitabine-loaded micelles on drug resistance caused by RRM1 overexpression.
    Biomaterials, 2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Piyanuch Wonganan, Hannah L. O’mary, Zhengrong Cui
    Abstract:

    Chemoresistance is a major issue for most gemcitabine-related chemotherapies. The overexpression of ribonucleotide reductase subunit M1 (RRM1) plays a key role in gemcitabine resistance. In this study, we synthesized a new highly Acid-sensitive amphiphilic micelle material by conjugating hydrophilic polyethylene glycol with a hydrophobic Stearic Acid Derivative (C18) using a hydrazone bond, which was named as PHC-2. A lipophilic prodrug of gemcitabine, 4-(N)-stearoyl gemcitabine (GemC18), was loaded into micelles prepared with PHC-2, a previously synthesized less Acid-sensitive PHC-1, and their Acid-insensitive counterpart, PAC. GemC18 loaded in Acid-sensitive micelles can overcome gemcitabine resistance, and GemC18 in the highly Acid-sensitive PHC-2 micelles was more cytotoxic than in the less Acid-sensitive PHC-1 micelles. Mechanistic studies revealed that upon cellular uptake and lysosomal delivery, GemC18 in the Acid-sensitive micelles was released and hydrolyzed more efficiently. Furthermore, GemC18 loaded in the highly Acid-sensitive PHC-2 micelles inhibited the expression of RRM1 and increased the level of gemcitabine triphosphate (dFdCTP) in gemcitabine resistant tumor cells. The strategy of delivering lipophilized nucleoside analogs using highly Acid-sensitive micelles may represent a new platform technology to increase the antitumor activity of nucleoside analogs and to overcome tumor cell resistance to them.

  • Lysosomal delivery of a lipophilic gemcitabine prodrug using novel Acid-sensitive micelles improved its antitumor activity.
    Bioconjugate chemistry, 2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Zhengrong Cui
    Abstract:

    Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer Acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly(ethylene glycol) (PEG) with a hydrophobic Stearic Acid Derivative (C18) using an Acid-sensitive hydrazone bond (PHC). An Acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the Acid-sensitive PHC micelles was more cytotoxic than in the Acid-insensitive PAC micelles, which may be attributed to the Acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16–F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activ...

  • Lysosomal Delivery of a Lipophilic Gemcitabine Prodrug Using Novel Acid-Sensitive Micelles Improved Its Antitumor Activity
    2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Zhengrong Cui
    Abstract:

    Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer Acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly­(ethylene glycol) (PEG) with a hydrophobic Stearic Acid Derivative (C18) using an Acid-sensitive hydrazone bond (PHC). An Acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the Acid-sensitive PHC micelles was more cytotoxic than in the Acid-insensitive PAC micelles, which may be attributed to the Acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16–F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activity than GemC18 or gemcitabine solution, likely because of the prolonged circulation time and increased tumor accumulation of the GemC18 by the micelles. Importantly, the in vivo antitumor activity of GemC18-loaded PHC micelles was significantly stronger than that of the PAC micelles, demonstrating the potential of the novel Acid-sensitive micelles as an anticancer drug delivery system

Saijie Zhu - One of the best experts on this subject based on the ideXlab platform.

  • The effect of the Acid-sensitivity of 4-(N)-stearoyl gemcitabine-loaded micelles on drug resistance caused by RRM1 overexpression.
    Biomaterials, 2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Piyanuch Wonganan, Hannah L. O’mary, Zhengrong Cui
    Abstract:

    Chemoresistance is a major issue for most gemcitabine-related chemotherapies. The overexpression of ribonucleotide reductase subunit M1 (RRM1) plays a key role in gemcitabine resistance. In this study, we synthesized a new highly Acid-sensitive amphiphilic micelle material by conjugating hydrophilic polyethylene glycol with a hydrophobic Stearic Acid Derivative (C18) using a hydrazone bond, which was named as PHC-2. A lipophilic prodrug of gemcitabine, 4-(N)-stearoyl gemcitabine (GemC18), was loaded into micelles prepared with PHC-2, a previously synthesized less Acid-sensitive PHC-1, and their Acid-insensitive counterpart, PAC. GemC18 loaded in Acid-sensitive micelles can overcome gemcitabine resistance, and GemC18 in the highly Acid-sensitive PHC-2 micelles was more cytotoxic than in the less Acid-sensitive PHC-1 micelles. Mechanistic studies revealed that upon cellular uptake and lysosomal delivery, GemC18 in the Acid-sensitive micelles was released and hydrolyzed more efficiently. Furthermore, GemC18 loaded in the highly Acid-sensitive PHC-2 micelles inhibited the expression of RRM1 and increased the level of gemcitabine triphosphate (dFdCTP) in gemcitabine resistant tumor cells. The strategy of delivering lipophilized nucleoside analogs using highly Acid-sensitive micelles may represent a new platform technology to increase the antitumor activity of nucleoside analogs and to overcome tumor cell resistance to them.

  • Lysosomal delivery of a lipophilic gemcitabine prodrug using novel Acid-sensitive micelles improved its antitumor activity.
    Bioconjugate chemistry, 2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Zhengrong Cui
    Abstract:

    Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer Acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly(ethylene glycol) (PEG) with a hydrophobic Stearic Acid Derivative (C18) using an Acid-sensitive hydrazone bond (PHC). An Acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the Acid-sensitive PHC micelles was more cytotoxic than in the Acid-insensitive PAC micelles, which may be attributed to the Acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16–F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activ...

  • Lysosomal Delivery of a Lipophilic Gemcitabine Prodrug Using Novel Acid-Sensitive Micelles Improved Its Antitumor Activity
    2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Zhengrong Cui
    Abstract:

    Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer Acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly­(ethylene glycol) (PEG) with a hydrophobic Stearic Acid Derivative (C18) using an Acid-sensitive hydrazone bond (PHC). An Acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the Acid-sensitive PHC micelles was more cytotoxic than in the Acid-insensitive PAC micelles, which may be attributed to the Acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16–F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activity than GemC18 or gemcitabine solution, likely because of the prolonged circulation time and increased tumor accumulation of the GemC18 by the micelles. Importantly, the in vivo antitumor activity of GemC18-loaded PHC micelles was significantly stronger than that of the PAC micelles, demonstrating the potential of the novel Acid-sensitive micelles as an anticancer drug delivery system

Dharmika S.p. Lansakara-p - One of the best experts on this subject based on the ideXlab platform.

  • The effect of the Acid-sensitivity of 4-(N)-stearoyl gemcitabine-loaded micelles on drug resistance caused by RRM1 overexpression.
    Biomaterials, 2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Piyanuch Wonganan, Hannah L. O’mary, Zhengrong Cui
    Abstract:

    Chemoresistance is a major issue for most gemcitabine-related chemotherapies. The overexpression of ribonucleotide reductase subunit M1 (RRM1) plays a key role in gemcitabine resistance. In this study, we synthesized a new highly Acid-sensitive amphiphilic micelle material by conjugating hydrophilic polyethylene glycol with a hydrophobic Stearic Acid Derivative (C18) using a hydrazone bond, which was named as PHC-2. A lipophilic prodrug of gemcitabine, 4-(N)-stearoyl gemcitabine (GemC18), was loaded into micelles prepared with PHC-2, a previously synthesized less Acid-sensitive PHC-1, and their Acid-insensitive counterpart, PAC. GemC18 loaded in Acid-sensitive micelles can overcome gemcitabine resistance, and GemC18 in the highly Acid-sensitive PHC-2 micelles was more cytotoxic than in the less Acid-sensitive PHC-1 micelles. Mechanistic studies revealed that upon cellular uptake and lysosomal delivery, GemC18 in the Acid-sensitive micelles was released and hydrolyzed more efficiently. Furthermore, GemC18 loaded in the highly Acid-sensitive PHC-2 micelles inhibited the expression of RRM1 and increased the level of gemcitabine triphosphate (dFdCTP) in gemcitabine resistant tumor cells. The strategy of delivering lipophilized nucleoside analogs using highly Acid-sensitive micelles may represent a new platform technology to increase the antitumor activity of nucleoside analogs and to overcome tumor cell resistance to them.

  • Lysosomal delivery of a lipophilic gemcitabine prodrug using novel Acid-sensitive micelles improved its antitumor activity.
    Bioconjugate chemistry, 2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Zhengrong Cui
    Abstract:

    Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer Acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly(ethylene glycol) (PEG) with a hydrophobic Stearic Acid Derivative (C18) using an Acid-sensitive hydrazone bond (PHC). An Acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the Acid-sensitive PHC micelles was more cytotoxic than in the Acid-insensitive PAC micelles, which may be attributed to the Acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16–F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activ...

  • Lysosomal Delivery of a Lipophilic Gemcitabine Prodrug Using Novel Acid-Sensitive Micelles Improved Its Antitumor Activity
    2012
    Co-Authors: Saijie Zhu, Dharmika S.p. Lansakara-p, Zhengrong Cui
    Abstract:

    Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer Acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly­(ethylene glycol) (PEG) with a hydrophobic Stearic Acid Derivative (C18) using an Acid-sensitive hydrazone bond (PHC). An Acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the Acid-sensitive PHC micelles was more cytotoxic than in the Acid-insensitive PAC micelles, which may be attributed to the Acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16–F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activity than GemC18 or gemcitabine solution, likely because of the prolonged circulation time and increased tumor accumulation of the GemC18 by the micelles. Importantly, the in vivo antitumor activity of GemC18-loaded PHC micelles was significantly stronger than that of the PAC micelles, demonstrating the potential of the novel Acid-sensitive micelles as an anticancer drug delivery system

Mauricio Rojas - One of the best experts on this subject based on the ideXlab platform.

  • Mononuclear phagocyte accumulates a Stearic Acid Derivative during differentiation into macrophages. Effects of Stearic Acid on macrophage differentiation and Mycobacterium tuberculosis control.
    Cellular immunology, 2016
    Co-Authors: Sergio Fabián Mosquera-restrepo, Ana Cecilia Caro, Carlos A Peláez-jaramillo, Mauricio Rojas
    Abstract:

    The fatty Acid composition of monocytes changes substantially during differentiation into macrophages, increasing the proportion of saturated fatty Acids. These changes prompted us to investigate whether fatty Acid accumulation in the extracellular milieu could affect the differentiation of bystander mononuclear phagocytes. An esterified fatty Acid Derivative, stearate, was the only fatty Acid that significantly increased in macrophage supernatants, and there were higher levels when cells differentiated in the presence of Mycobacterium tuberculosis H37Rv or purified protein Derivative (PPD). Exogenous Stearic Acid enhanced the expression of HLA-DR and CD64; there was also accumulation of IL-12, TNF-α, IL-6, MIP-1 α and β and a reduction in MCP-1 and the bacterial load. These results suggested that during differentiation, a Derivative of Stearic Acid, which promotes the process as well as the effector mechanisms of phagocytes against the mycobacterium, accumulates in the cell supernatants.

Sergio Fabián Mosquera-restrepo - One of the best experts on this subject based on the ideXlab platform.

  • Mononuclear phagocyte accumulates a Stearic Acid Derivative during differentiation into macrophages. Effects of Stearic Acid on macrophage differentiation and Mycobacterium tuberculosis control.
    Cellular immunology, 2016
    Co-Authors: Sergio Fabián Mosquera-restrepo, Ana Cecilia Caro, Carlos A Peláez-jaramillo, Mauricio Rojas
    Abstract:

    The fatty Acid composition of monocytes changes substantially during differentiation into macrophages, increasing the proportion of saturated fatty Acids. These changes prompted us to investigate whether fatty Acid accumulation in the extracellular milieu could affect the differentiation of bystander mononuclear phagocytes. An esterified fatty Acid Derivative, stearate, was the only fatty Acid that significantly increased in macrophage supernatants, and there were higher levels when cells differentiated in the presence of Mycobacterium tuberculosis H37Rv or purified protein Derivative (PPD). Exogenous Stearic Acid enhanced the expression of HLA-DR and CD64; there was also accumulation of IL-12, TNF-α, IL-6, MIP-1 α and β and a reduction in MCP-1 and the bacterial load. These results suggested that during differentiation, a Derivative of Stearic Acid, which promotes the process as well as the effector mechanisms of phagocytes against the mycobacterium, accumulates in the cell supernatants.