The Experts below are selected from a list of 7488 Experts worldwide ranked by ideXlab platform
Kui Luo - One of the best experts on this subject based on the ideXlab platform.
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enzyme responsive peptide dendrimer gemcitabine conjugate as a controlled release Drug Delivery Vehicle with enhanced antitumor efficacy
Acta Biomaterialia, 2017Co-Authors: Kui Luo, Dayi Pan, Chengyuan Zhang, Ashika Bains, Nicholas Guys, Hongyan Zhu, Qiyong GongAbstract:Abstract Stimuli-responsive peptide dendrimer-Drug conjugates have presented significant potential for cancer therapy. To develop an effective nanoscale chemotherapeutic proDrug, we developed a novel enzyme-responsive PEGylated lysine peptide dendrimer-gemcitabine conjugate (Dendrimer-GEM) based nanoparticle via the highly efficient click reaction. Owing to the glycyl phenylalanyl leucyl glycine tetra-peptide (GFLG) as an enzyme-cleavable linker to conjugate gemcitabine (GEM), the prepared nanoparticles were able to release Drug significantly faster in the tumor cellular environments, which specifically contains secreted Cathepsin B, quantifiably more than 80% GEM was released with Cathepsin B compared to the condition without Cathepsin B at 24 h. This nanoparticle demonstrated enhanced antitumor efficacy in a 4T1 murine breast cancer model without obvious systemic toxicity, resulting in significantly suppressed relative tumor volumes (86.17 ± 38.27%) and a 2-fold higher value of tumor growth inhibition (∼90%) than GEM·HCl treatment. These results suggest that the PEGylated peptide dendrimer-gemcitabine conjugate can be an effective antitumor agent for breast cancer therapy. Statement of Significance We found that the functionalized dendrimer based nanoscale Drug Delivery Vehicles exhibited enhanced therapeutic indexes and reduced toxicity as compared to the free Drug gemcitabine. Compared with current nanoparticles, such as dendritic anticancer Drug Delivery systems, the new design was capable of self-assembling into nanoscale particles with sizes of about 80–110 nm, which is suitable as antitumor Drug Delivery Vehicle due to the potential longer intravascular half-life and higher accumulation in tumor tissue via EPR effect. Owing to the optimized architecture, the system was given the enzyme-responsive Drug release feature, and showed excellent antitumor activity on the 4T1 breast tumor model due to the evidences from tumor growth curves, immunohistochemical analysis and confocal laser scanning microscopy. Meanwhile, no significant side effect was observed by histological analysis. This study demonstrated that PEGylated peptide dendritic architecture may be used as efficient and safe nanoscale Drug Delivery Vehicle for cancer therapy.
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a stimuli responsive janus peptide dendron Drug conjugate as a safe and nanoscale Drug Delivery Vehicle for breast cancer therapy
Journal of Materials Chemistry B, 2016Co-Authors: Chunhua Guo, Zhenyu Duan, Kui LuoAbstract:Smart nanoscale Drug Delivery systems have been investigated as potential candidates for Drug Delivery Vehicles. Here, we used a breast cancer model to determine if the enzyme-responsive Janus dendron (mPEGylated dendron–PVGLIG–DOX) conjugate-based nanoscale system would be an effective and safe Drug Delivery Vehicle for chemotherapy. To this end, we prepared and characterized the matrix metalloprotease-2 (MMP-2)/MMP-9-sensitive linker of the proline–valine–glycine–leucine–isoleucine–glycine (Pro–Val–Gly–Leu–Ile–Gly, PVGLIG) oligopeptide via a convenient and fast liquid-phase synthesis. Second, using a rational design strategy, the Janus dendron (Boc–G2L–G3L–OMe) was successfully modified with mPEG and PVGLIG–DOX via a two-step highly efficient copper-catalyzed alkyne–azide click cycloaddition (CuAAC) reaction. Morphology studies such as dynamic light scattering, scanning electron microscopy, and atomic force microscopy were performed to confirm that the Janus mPEGylated dendron–PVGLIG–DOX conjugate self-assembled into compact nanoparticles with a slightly negatively charged surface. The nanoscale system, which included nanoparticles with 4.0 wt% (weight percent) of doxorubicin (DOX), was analyzed using ultraviolet-visible absorption spectra, fluorescence emission spectra, and matrix assisted laser desorption/ionization time-of-flight. Nanoscale systems incubated with exogenous MMP-2 killed breast cancer cells were more effective than those lacking MMP-2. Compared to free DOX, the nanoscale system substantially reduced the side effects accompanied by a similar antitumor efficacy. Moreover, it had minimal systemic toxicities, especially DOX-induced toxicities to the normal organs of both tumor bearing and healthy mice, as determined by changes in the body weight and histological analysis. These data demonstrate that the Janus dendron Drug conjugate-based nanoscale system may be an effective chemotherapy Delivery Vehicle for breast cancer.
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amphiphilic peptide dendritic copolymer doxorubicin nanoscale conjugate self assembled to enzyme responsive anti cancer agent
Biomaterials, 2014Co-Authors: Kui Luo, Chunhua Guo, Dayi PanAbstract:Peptide dendrimer Drug conjugate based nanoparticles are recently developed as a potential candidate for Drug Delivery Vehicle. In this study, we prepared and characterized the enzyme-sensitive amphiphilc mPEGylated dendron-GFLG-DOX conjugate via two-step highly efficient click reaction. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the mPEGylated dendron-GFLG-DOX conjugate self-assembled into compact nanoparticles with negatively charged surface. The nanoparticles with 9.62 wt% (weight percent) of DOX showed enzyme-sensitive property by Drug release tests. The nanoparticles were shown to effectively kill cancer cells in vitro. The fluorescent image indicated that the nanoparticles could accumulate and retain within tumor for a long time. Moreover, the nanoparticles substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis of the 4T1 murine breast cancer model confirmed as the evidences from tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The nanoparticles reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shifts and histological analysis. Therefore, the mPEGylated dendron-GFLG-DOX conjugate based nanoparticle serves as a potential Drug Delivery Vehicle for breast cancer therapy.
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dendrimer doxorubicin conjugate as enzyme sensitive and polymeric nanoscale Drug Delivery Vehicle for ovarian cancer therapy
Polymer Chemistry, 2014Co-Authors: Chengyuan Zhang, Kui Luo, Chunhua Guo, Dayi Pan, Xiuli ZhengAbstract:Peptide dendrimer-based nanoparticles have presented significant potential as candidates for Drug Delivery system. In this study, we synthesized and characterized enzyme-responsive mPEGylated peptide dendrimer–GFLG–doxorubicin conjugate (dendrimer–GFLG–DOX) as a chemotherapeutic Drug Delivery nano-carrier via a two-step highly efficient copper-catalyzed alkyne–azide click cycloaddition (CuAAC) reaction. The tetra-peptide sequence Gly–Phe–Leu–Gly (GFLG) was explored as an enzyme-responsive linker to connect the doxorubicin (DOX) to the periphery of mPEGylated peptide dendrimer. The dendrimer–GFLG–DOX was capable of self-assembling into nanoparticle, which was proven by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. Compared to the free Drug DOX, the dendrimer–GFLG–DOX conjugate based nanoparticle demonstrated higher accumulation and retention within SKOV-3 ovarian tumor tissue, resulting in a higher antitumor activity as evidenced from tumor growth curves, tumor growth inhibition analysis, immunohistochemical assessment and in vivo imaging. Moreover, no obvious systemic toxicity was observed via histological assessment. Thus, the mPEGylated peptide dendrimer–DOX conjugate-based nanoparticle may be a promising candidate as a nanoscale and enzyme-sensitive Drug Delivery Vehicle for ovarian cancer therapy.
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peptide dendrimer doxorubicin conjugate based nanoparticles as an enzyme responsive Drug Delivery system for cancer therapy
Advanced Healthcare Materials, 2014Co-Authors: Chengyuan Zhang, Wenchuan She, Kui Luo, Chunhua Guo, Dayi Pan, Yang YangAbstract:Peptide dendrimers have shown promise as an attractive platform for Drug Delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive Drug Delivery Vehicle. The Drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale Drug Delivery Vehicle for the breast cancer therapy.
Chunhua Guo - One of the best experts on this subject based on the ideXlab platform.
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a stimuli responsive janus peptide dendron Drug conjugate as a safe and nanoscale Drug Delivery Vehicle for breast cancer therapy
Journal of Materials Chemistry B, 2016Co-Authors: Chunhua Guo, Zhenyu Duan, Kui LuoAbstract:Smart nanoscale Drug Delivery systems have been investigated as potential candidates for Drug Delivery Vehicles. Here, we used a breast cancer model to determine if the enzyme-responsive Janus dendron (mPEGylated dendron–PVGLIG–DOX) conjugate-based nanoscale system would be an effective and safe Drug Delivery Vehicle for chemotherapy. To this end, we prepared and characterized the matrix metalloprotease-2 (MMP-2)/MMP-9-sensitive linker of the proline–valine–glycine–leucine–isoleucine–glycine (Pro–Val–Gly–Leu–Ile–Gly, PVGLIG) oligopeptide via a convenient and fast liquid-phase synthesis. Second, using a rational design strategy, the Janus dendron (Boc–G2L–G3L–OMe) was successfully modified with mPEG and PVGLIG–DOX via a two-step highly efficient copper-catalyzed alkyne–azide click cycloaddition (CuAAC) reaction. Morphology studies such as dynamic light scattering, scanning electron microscopy, and atomic force microscopy were performed to confirm that the Janus mPEGylated dendron–PVGLIG–DOX conjugate self-assembled into compact nanoparticles with a slightly negatively charged surface. The nanoscale system, which included nanoparticles with 4.0 wt% (weight percent) of doxorubicin (DOX), was analyzed using ultraviolet-visible absorption spectra, fluorescence emission spectra, and matrix assisted laser desorption/ionization time-of-flight. Nanoscale systems incubated with exogenous MMP-2 killed breast cancer cells were more effective than those lacking MMP-2. Compared to free DOX, the nanoscale system substantially reduced the side effects accompanied by a similar antitumor efficacy. Moreover, it had minimal systemic toxicities, especially DOX-induced toxicities to the normal organs of both tumor bearing and healthy mice, as determined by changes in the body weight and histological analysis. These data demonstrate that the Janus dendron Drug conjugate-based nanoscale system may be an effective chemotherapy Delivery Vehicle for breast cancer.
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amphiphilic peptide dendritic copolymer doxorubicin nanoscale conjugate self assembled to enzyme responsive anti cancer agent
Biomaterials, 2014Co-Authors: Kui Luo, Chunhua Guo, Dayi PanAbstract:Peptide dendrimer Drug conjugate based nanoparticles are recently developed as a potential candidate for Drug Delivery Vehicle. In this study, we prepared and characterized the enzyme-sensitive amphiphilc mPEGylated dendron-GFLG-DOX conjugate via two-step highly efficient click reaction. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the mPEGylated dendron-GFLG-DOX conjugate self-assembled into compact nanoparticles with negatively charged surface. The nanoparticles with 9.62 wt% (weight percent) of DOX showed enzyme-sensitive property by Drug release tests. The nanoparticles were shown to effectively kill cancer cells in vitro. The fluorescent image indicated that the nanoparticles could accumulate and retain within tumor for a long time. Moreover, the nanoparticles substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis of the 4T1 murine breast cancer model confirmed as the evidences from tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The nanoparticles reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shifts and histological analysis. Therefore, the mPEGylated dendron-GFLG-DOX conjugate based nanoparticle serves as a potential Drug Delivery Vehicle for breast cancer therapy.
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dendrimer doxorubicin conjugate as enzyme sensitive and polymeric nanoscale Drug Delivery Vehicle for ovarian cancer therapy
Polymer Chemistry, 2014Co-Authors: Chengyuan Zhang, Kui Luo, Chunhua Guo, Dayi Pan, Xiuli ZhengAbstract:Peptide dendrimer-based nanoparticles have presented significant potential as candidates for Drug Delivery system. In this study, we synthesized and characterized enzyme-responsive mPEGylated peptide dendrimer–GFLG–doxorubicin conjugate (dendrimer–GFLG–DOX) as a chemotherapeutic Drug Delivery nano-carrier via a two-step highly efficient copper-catalyzed alkyne–azide click cycloaddition (CuAAC) reaction. The tetra-peptide sequence Gly–Phe–Leu–Gly (GFLG) was explored as an enzyme-responsive linker to connect the doxorubicin (DOX) to the periphery of mPEGylated peptide dendrimer. The dendrimer–GFLG–DOX was capable of self-assembling into nanoparticle, which was proven by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. Compared to the free Drug DOX, the dendrimer–GFLG–DOX conjugate based nanoparticle demonstrated higher accumulation and retention within SKOV-3 ovarian tumor tissue, resulting in a higher antitumor activity as evidenced from tumor growth curves, tumor growth inhibition analysis, immunohistochemical assessment and in vivo imaging. Moreover, no obvious systemic toxicity was observed via histological assessment. Thus, the mPEGylated peptide dendrimer–DOX conjugate-based nanoparticle may be a promising candidate as a nanoscale and enzyme-sensitive Drug Delivery Vehicle for ovarian cancer therapy.
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peptide dendrimer doxorubicin conjugate based nanoparticles as an enzyme responsive Drug Delivery system for cancer therapy
Advanced Healthcare Materials, 2014Co-Authors: Chengyuan Zhang, Wenchuan She, Kui Luo, Chunhua Guo, Dayi Pan, Yang YangAbstract:Peptide dendrimers have shown promise as an attractive platform for Drug Delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive Drug Delivery Vehicle. The Drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale Drug Delivery Vehicle for the breast cancer therapy.
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dendronized heparin doxorubicin conjugate based nanoparticle as ph responsive Drug Delivery system for cancer therapy
Biomaterials, 2013Co-Authors: Wenchuan She, Kui Luo, Chunhua Guo, Yanyan Geng, Gang Wang, Ning Li, Zhongwei GuAbstract:Abstract Heparin Drug conjugates are currently investigated as excellent candidates for Drug Delivery Vehicles. In this study, we report the preparation and characterization of dendronized heparin–doxorubicin (heparin–DOX) conjugate as pH-sensitive Drug Delivery Vehicle by combination of the features of dendrimer and heparin. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the dendronized heparin–DOX conjugate self–assembled into compact nanoparticles with negatively charged surface. The nanoparticles with 9.0 wt% (weight percent) of doxorubicin (DOX) showed pH-sensitive property due to the faster Drug release rate at pH 5.0 and slow release rate at pH 7.4 aqueous. The nanoparticles were shown to effectively kill cancer cells in vitro. Notablely, the nanoparticles resulted in strong antitumor activity, high antiangiogenesis effects and induced apoptosis on the 4T1 breast tumor model due to the evidences from mice weight shifts, tumor weights, tumor growth curves, immunohistochemical assessment and histological analysis. It's also noteworthy that dendronized heparin and its nanoparticle with Drug demonstrated no significant toxicity to healthy organs of both tumor–bearing and healthy mice, which was confirmed by histological analysis compared with free Drug DOX. The dendronized heparin–DOX conjugate based nanopatilce with high antitumor activity and low side effects may be therefore a potential nanoscale Drug Delivery Vehicle for breast cancer therapy.
Dayi Pan - One of the best experts on this subject based on the ideXlab platform.
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enzyme responsive peptide dendrimer gemcitabine conjugate as a controlled release Drug Delivery Vehicle with enhanced antitumor efficacy
Acta Biomaterialia, 2017Co-Authors: Kui Luo, Dayi Pan, Chengyuan Zhang, Ashika Bains, Nicholas Guys, Hongyan Zhu, Qiyong GongAbstract:Abstract Stimuli-responsive peptide dendrimer-Drug conjugates have presented significant potential for cancer therapy. To develop an effective nanoscale chemotherapeutic proDrug, we developed a novel enzyme-responsive PEGylated lysine peptide dendrimer-gemcitabine conjugate (Dendrimer-GEM) based nanoparticle via the highly efficient click reaction. Owing to the glycyl phenylalanyl leucyl glycine tetra-peptide (GFLG) as an enzyme-cleavable linker to conjugate gemcitabine (GEM), the prepared nanoparticles were able to release Drug significantly faster in the tumor cellular environments, which specifically contains secreted Cathepsin B, quantifiably more than 80% GEM was released with Cathepsin B compared to the condition without Cathepsin B at 24 h. This nanoparticle demonstrated enhanced antitumor efficacy in a 4T1 murine breast cancer model without obvious systemic toxicity, resulting in significantly suppressed relative tumor volumes (86.17 ± 38.27%) and a 2-fold higher value of tumor growth inhibition (∼90%) than GEM·HCl treatment. These results suggest that the PEGylated peptide dendrimer-gemcitabine conjugate can be an effective antitumor agent for breast cancer therapy. Statement of Significance We found that the functionalized dendrimer based nanoscale Drug Delivery Vehicles exhibited enhanced therapeutic indexes and reduced toxicity as compared to the free Drug gemcitabine. Compared with current nanoparticles, such as dendritic anticancer Drug Delivery systems, the new design was capable of self-assembling into nanoscale particles with sizes of about 80–110 nm, which is suitable as antitumor Drug Delivery Vehicle due to the potential longer intravascular half-life and higher accumulation in tumor tissue via EPR effect. Owing to the optimized architecture, the system was given the enzyme-responsive Drug release feature, and showed excellent antitumor activity on the 4T1 breast tumor model due to the evidences from tumor growth curves, immunohistochemical analysis and confocal laser scanning microscopy. Meanwhile, no significant side effect was observed by histological analysis. This study demonstrated that PEGylated peptide dendritic architecture may be used as efficient and safe nanoscale Drug Delivery Vehicle for cancer therapy.
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amphiphilic peptide dendritic copolymer doxorubicin nanoscale conjugate self assembled to enzyme responsive anti cancer agent
Biomaterials, 2014Co-Authors: Kui Luo, Chunhua Guo, Dayi PanAbstract:Peptide dendrimer Drug conjugate based nanoparticles are recently developed as a potential candidate for Drug Delivery Vehicle. In this study, we prepared and characterized the enzyme-sensitive amphiphilc mPEGylated dendron-GFLG-DOX conjugate via two-step highly efficient click reaction. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the mPEGylated dendron-GFLG-DOX conjugate self-assembled into compact nanoparticles with negatively charged surface. The nanoparticles with 9.62 wt% (weight percent) of DOX showed enzyme-sensitive property by Drug release tests. The nanoparticles were shown to effectively kill cancer cells in vitro. The fluorescent image indicated that the nanoparticles could accumulate and retain within tumor for a long time. Moreover, the nanoparticles substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis of the 4T1 murine breast cancer model confirmed as the evidences from tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The nanoparticles reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shifts and histological analysis. Therefore, the mPEGylated dendron-GFLG-DOX conjugate based nanoparticle serves as a potential Drug Delivery Vehicle for breast cancer therapy.
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dendrimer doxorubicin conjugate as enzyme sensitive and polymeric nanoscale Drug Delivery Vehicle for ovarian cancer therapy
Polymer Chemistry, 2014Co-Authors: Chengyuan Zhang, Kui Luo, Chunhua Guo, Dayi Pan, Xiuli ZhengAbstract:Peptide dendrimer-based nanoparticles have presented significant potential as candidates for Drug Delivery system. In this study, we synthesized and characterized enzyme-responsive mPEGylated peptide dendrimer–GFLG–doxorubicin conjugate (dendrimer–GFLG–DOX) as a chemotherapeutic Drug Delivery nano-carrier via a two-step highly efficient copper-catalyzed alkyne–azide click cycloaddition (CuAAC) reaction. The tetra-peptide sequence Gly–Phe–Leu–Gly (GFLG) was explored as an enzyme-responsive linker to connect the doxorubicin (DOX) to the periphery of mPEGylated peptide dendrimer. The dendrimer–GFLG–DOX was capable of self-assembling into nanoparticle, which was proven by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. Compared to the free Drug DOX, the dendrimer–GFLG–DOX conjugate based nanoparticle demonstrated higher accumulation and retention within SKOV-3 ovarian tumor tissue, resulting in a higher antitumor activity as evidenced from tumor growth curves, tumor growth inhibition analysis, immunohistochemical assessment and in vivo imaging. Moreover, no obvious systemic toxicity was observed via histological assessment. Thus, the mPEGylated peptide dendrimer–DOX conjugate-based nanoparticle may be a promising candidate as a nanoscale and enzyme-sensitive Drug Delivery Vehicle for ovarian cancer therapy.
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peptide dendrimer doxorubicin conjugate based nanoparticles as an enzyme responsive Drug Delivery system for cancer therapy
Advanced Healthcare Materials, 2014Co-Authors: Chengyuan Zhang, Wenchuan She, Kui Luo, Chunhua Guo, Dayi Pan, Yang YangAbstract:Peptide dendrimers have shown promise as an attractive platform for Drug Delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive Drug Delivery Vehicle. The Drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale Drug Delivery Vehicle for the breast cancer therapy.
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biodegradable and amphiphilic block copolymer doxorubicin conjugate as polymeric nanoscale Drug Delivery Vehicle for breast cancer therapy
Biomaterials, 2013Co-Authors: Yang Yang, Dayi Pan, Kui LuoAbstract:Polymeric nanoparticles have shown great promise as attractive Vehicles for Drug Delivery. In this study, we designed, prepared and characterized biodegradable amphiphilic triblock HPMA copolymer-doxorubicin (copolymer-DOX) conjugate based nanoparticle as enzyme-sensitive Drug Delivery Vehicle. The enzyme-sensitive peptide GFLGKGLFG was introduced to the main chain of the copolymer with hydrophilic and hydrophobic blocks. The triblock HPMA polymer-DOX conjugate with high molecules (Mw 90 kDa) can be degraded to product with low molecule weight (Mw 44 kDa) below the renal threshold. The copolymer-DOX conjugate can self-assemble into compact nanoparticle, which was characterized by scanning electron microscope (SEM) and atomic force microscope (AFM) studies. This polymeric nanoparticle substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis on the 4T1 murine breast cancer model confirmed by the evidences from mice weight shifts, tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The in vivo toxicity evaluation demonstrated that the polymeric nanoparticle reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shift, blood routine test and histological analysis. Therefore, the triblock HPMA copolymer-DOX conjugate based nanoparticle is promising as a potential Drug Delivery Vehicle for breast cancer therapy.
Chengyuan Zhang - One of the best experts on this subject based on the ideXlab platform.
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enzyme responsive peptide dendrimer gemcitabine conjugate as a controlled release Drug Delivery Vehicle with enhanced antitumor efficacy
Acta Biomaterialia, 2017Co-Authors: Kui Luo, Dayi Pan, Chengyuan Zhang, Ashika Bains, Nicholas Guys, Hongyan Zhu, Qiyong GongAbstract:Abstract Stimuli-responsive peptide dendrimer-Drug conjugates have presented significant potential for cancer therapy. To develop an effective nanoscale chemotherapeutic proDrug, we developed a novel enzyme-responsive PEGylated lysine peptide dendrimer-gemcitabine conjugate (Dendrimer-GEM) based nanoparticle via the highly efficient click reaction. Owing to the glycyl phenylalanyl leucyl glycine tetra-peptide (GFLG) as an enzyme-cleavable linker to conjugate gemcitabine (GEM), the prepared nanoparticles were able to release Drug significantly faster in the tumor cellular environments, which specifically contains secreted Cathepsin B, quantifiably more than 80% GEM was released with Cathepsin B compared to the condition without Cathepsin B at 24 h. This nanoparticle demonstrated enhanced antitumor efficacy in a 4T1 murine breast cancer model without obvious systemic toxicity, resulting in significantly suppressed relative tumor volumes (86.17 ± 38.27%) and a 2-fold higher value of tumor growth inhibition (∼90%) than GEM·HCl treatment. These results suggest that the PEGylated peptide dendrimer-gemcitabine conjugate can be an effective antitumor agent for breast cancer therapy. Statement of Significance We found that the functionalized dendrimer based nanoscale Drug Delivery Vehicles exhibited enhanced therapeutic indexes and reduced toxicity as compared to the free Drug gemcitabine. Compared with current nanoparticles, such as dendritic anticancer Drug Delivery systems, the new design was capable of self-assembling into nanoscale particles with sizes of about 80–110 nm, which is suitable as antitumor Drug Delivery Vehicle due to the potential longer intravascular half-life and higher accumulation in tumor tissue via EPR effect. Owing to the optimized architecture, the system was given the enzyme-responsive Drug release feature, and showed excellent antitumor activity on the 4T1 breast tumor model due to the evidences from tumor growth curves, immunohistochemical analysis and confocal laser scanning microscopy. Meanwhile, no significant side effect was observed by histological analysis. This study demonstrated that PEGylated peptide dendritic architecture may be used as efficient and safe nanoscale Drug Delivery Vehicle for cancer therapy.
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dendrimer doxorubicin conjugate as enzyme sensitive and polymeric nanoscale Drug Delivery Vehicle for ovarian cancer therapy
Polymer Chemistry, 2014Co-Authors: Chengyuan Zhang, Kui Luo, Chunhua Guo, Dayi Pan, Xiuli ZhengAbstract:Peptide dendrimer-based nanoparticles have presented significant potential as candidates for Drug Delivery system. In this study, we synthesized and characterized enzyme-responsive mPEGylated peptide dendrimer–GFLG–doxorubicin conjugate (dendrimer–GFLG–DOX) as a chemotherapeutic Drug Delivery nano-carrier via a two-step highly efficient copper-catalyzed alkyne–azide click cycloaddition (CuAAC) reaction. The tetra-peptide sequence Gly–Phe–Leu–Gly (GFLG) was explored as an enzyme-responsive linker to connect the doxorubicin (DOX) to the periphery of mPEGylated peptide dendrimer. The dendrimer–GFLG–DOX was capable of self-assembling into nanoparticle, which was proven by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. Compared to the free Drug DOX, the dendrimer–GFLG–DOX conjugate based nanoparticle demonstrated higher accumulation and retention within SKOV-3 ovarian tumor tissue, resulting in a higher antitumor activity as evidenced from tumor growth curves, tumor growth inhibition analysis, immunohistochemical assessment and in vivo imaging. Moreover, no obvious systemic toxicity was observed via histological assessment. Thus, the mPEGylated peptide dendrimer–DOX conjugate-based nanoparticle may be a promising candidate as a nanoscale and enzyme-sensitive Drug Delivery Vehicle for ovarian cancer therapy.
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peptide dendrimer doxorubicin conjugate based nanoparticles as an enzyme responsive Drug Delivery system for cancer therapy
Advanced Healthcare Materials, 2014Co-Authors: Chengyuan Zhang, Wenchuan She, Kui Luo, Chunhua Guo, Dayi Pan, Yang YangAbstract:Peptide dendrimers have shown promise as an attractive platform for Drug Delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive Drug Delivery Vehicle. The Drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale Drug Delivery Vehicle for the breast cancer therapy.
Shaomin Shuang - One of the best experts on this subject based on the ideXlab platform.
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facile fabrication route of janus gold mesoporous silica nanocarriers with dual Drug Delivery for tumor therapy
ACS Biomaterials Science & Engineering, 2020Co-Authors: Yang Xing, Ying Zhou, Yan Zhang, Caihong Zhang, Xu Deng, Chuan Dong, Shaomin ShuangAbstract:CoDelivery of Drugs using multifunctional nanoplatforms with anisotropic properties can produce synergistic effects and improve the antitumor activity of the Drugs. In this work, Janus gold-mesoporous silica nanoparticles have been successfully synthesized via the Pickering emulsion method. The obtained Janus nanoparticles were further selectively assembled with thiol-β-cyclodextrin as a Drug Delivery Vehicle for paclitaxel on gold domains, while the other mesoporous silica side with a mesoporous structure served as a Drug Delivery Vehicle for doxorubicin. These synthesized Janus nanoparticles possess pH and near-infrared (NIR) dual-responsive release properties. Furthermore, the tumor-bearing mice treated with dual-Drug-loaded Janus nanoparticles showed obvious tumor inhibition than single-Drug-loaded ones. Histological analysis reveals no pathological changes in the vital organs of the mice. The outcome demonstrated that dual-Drug-loaded Janus gold-mesoporous silica nanoparticles possessed a high therap...
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facile fabrication route of janus gold mesoporous silica nanocarriers with dual Drug Delivery for tumor therapy
ACS Biomaterials Science & Engineering, 2020Co-Authors: Yang Xing, Ying Zhou, Yan Zhang, Caihong Zhang, Xu Deng, Chuan Dong, Shaomin ShuangAbstract:CoDelivery of Drugs using multifunctional nanoplatforms with anisotropic properties can produce synergistic effects and improve the antitumor activity of the Drugs. In this work, Janus gold-mesoporous silica nanoparticles have been successfully synthesized via the Pickering emulsion method. The obtained Janus nanoparticles were further selectively assembled with thiol-β-cyclodextrin as a Drug Delivery Vehicle for paclitaxel on gold domains, while the other mesoporous silica side with a mesoporous structure served as a Drug Delivery Vehicle for doxorubicin. These synthesized Janus nanoparticles possess pH and near-infrared (NIR) dual-responsive release properties. Furthermore, the tumor-bearing mice treated with dual-Drug-loaded Janus nanoparticles showed obvious tumor inhibition than single-Drug-loaded ones. Histological analysis reveals no pathological changes in the vital organs of the mice. The outcome demonstrated that dual-Drug-loaded Janus gold-mesoporous silica nanoparticles possessed a high therapeutic efficiency and excellent biocompatibility both in vitro and in vivo and could be used as an effective candidate for cancer therapeutics.
