Doxorubicin conjugated AuNP/biopolymer composites facilitate cell cycle regulation and exhibit superior tumor suppression potential in KRAS mutant colorectal cancer

•AuNP/biopolymer therapeutic system with doxorubicin was designed and synthesized.•The system was characterized by UV spectrum, TEM, and zeta potential measurement.•Cancer cells were examined by MTT and cell cycle assays after the treatment.•Our system exhibits superior tumor suppression potential i...

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Veröffentlicht in:Journal of biotechnology 2019-12, Vol.306, p.149-158
Hauptverfasser: Hung, Wei-Hung, Zheng, Jia-Huei, Lee, Kuen-Chan, Cho, Er-Chieh
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creator Hung, Wei-Hung
Zheng, Jia-Huei
Lee, Kuen-Chan
Cho, Er-Chieh
description •AuNP/biopolymer therapeutic system with doxorubicin was designed and synthesized.•The system was characterized by UV spectrum, TEM, and zeta potential measurement.•Cancer cells were examined by MTT and cell cycle assays after the treatment.•Our system exhibits superior tumor suppression potential in the animal model. Colorectal cancer is a leading cause of death in the world. Despite the progress in therapeutic development, there are still challenges in clinical practice. Nanomedicine has emerged as a solution to enhance traditional therapy. Gold nanoparticles (AuNP) have been demonstrated as potential appliance in treating cancers, yet few studies investigated the capacity of biopolymer-conjugated AuNP in colon cancer as well as examined the system in both cancer cell line and animal models. In this study, we designed the AuNP/biopolymer composite therapeutic system with a chemotherapy agent, doxorubicin (DOX). Two composites with different drug load were applied (referred to as AuPPPyA and AuPPPyB). The composites were characterized by UV spectrum, transmission electron microscope (TEM), zeta potential measurement, and cell cycle analysis. Both therapeutic systems exhibited superior cytotoxic effects compared to DOX alone group. Compatible results were also demonstrated in vivo, as tumor inhibition rate were 46.2% in AuPPPyA and 66.4% in AuPPPyB, which were both higher than that of DOX alone (30%). Cell cycle regulation mediated by our composites was also examined in our study. In conclusion, our data demonstrated that AuNP/biopolymer composites are powerful in treating KRAS gene mutated colorectal cancer, and the system could potentially contribute to other clinical refractory diseases in the future.
doi_str_mv 10.1016/j.jbiotec.2019.09.015
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Colorectal cancer is a leading cause of death in the world. Despite the progress in therapeutic development, there are still challenges in clinical practice. Nanomedicine has emerged as a solution to enhance traditional therapy. Gold nanoparticles (AuNP) have been demonstrated as potential appliance in treating cancers, yet few studies investigated the capacity of biopolymer-conjugated AuNP in colon cancer as well as examined the system in both cancer cell line and animal models. In this study, we designed the AuNP/biopolymer composite therapeutic system with a chemotherapy agent, doxorubicin (DOX). Two composites with different drug load were applied (referred to as AuPPPyA and AuPPPyB). The composites were characterized by UV spectrum, transmission electron microscope (TEM), zeta potential measurement, and cell cycle analysis. Both therapeutic systems exhibited superior cytotoxic effects compared to DOX alone group. Compatible results were also demonstrated in vivo, as tumor inhibition rate were 46.2% in AuPPPyA and 66.4% in AuPPPyB, which were both higher than that of DOX alone (30%). Cell cycle regulation mediated by our composites was also examined in our study. In conclusion, our data demonstrated that AuNP/biopolymer composites are powerful in treating KRAS gene mutated colorectal cancer, and the system could potentially contribute to other clinical refractory diseases in the future.</description><identifier>ISSN: 0168-1656</identifier><identifier>EISSN: 1873-4863</identifier><identifier>DOI: 10.1016/j.jbiotec.2019.09.015</identifier><identifier>PMID: 31568802</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Biopolymer ; Biopolymers - chemistry ; Cell Cycle Checkpoints - drug effects ; Cell cycle regulation ; Cell Line, Tumor ; Cell Survival - drug effects ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Doxorubicin - chemistry ; Doxorubicin - pharmacology ; Drug Delivery Systems ; Gold - chemistry ; Gold - pharmacology ; Gold nanoparticles (AuNP) ; Humans ; KRAS mutant colorectal cancer ; Metal Nanoparticles - chemistry ; Mice, Nude ; Mutation ; Proto-Oncogene Proteins p21(ras) - genetics ; Tumor suppression ; Xenograft Model Antitumor Assays</subject><ispartof>Journal of biotechnology, 2019-12, Vol.306, p.149-158</ispartof><rights>2019</rights><rights>Copyright © 2019. 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Colorectal cancer is a leading cause of death in the world. Despite the progress in therapeutic development, there are still challenges in clinical practice. Nanomedicine has emerged as a solution to enhance traditional therapy. Gold nanoparticles (AuNP) have been demonstrated as potential appliance in treating cancers, yet few studies investigated the capacity of biopolymer-conjugated AuNP in colon cancer as well as examined the system in both cancer cell line and animal models. In this study, we designed the AuNP/biopolymer composite therapeutic system with a chemotherapy agent, doxorubicin (DOX). Two composites with different drug load were applied (referred to as AuPPPyA and AuPPPyB). The composites were characterized by UV spectrum, transmission electron microscope (TEM), zeta potential measurement, and cell cycle analysis. Both therapeutic systems exhibited superior cytotoxic effects compared to DOX alone group. Compatible results were also demonstrated in vivo, as tumor inhibition rate were 46.2% in AuPPPyA and 66.4% in AuPPPyB, which were both higher than that of DOX alone (30%). Cell cycle regulation mediated by our composites was also examined in our study. 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Zheng, Jia-Huei ; Lee, Kuen-Chan ; Cho, Er-Chieh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-6d99f34c4983fe17e56f8f1e4505a17698adf821e0e6f9dcc2276854b93722103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biopolymer</topic><topic>Biopolymers - chemistry</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell cycle regulation</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Doxorubicin - chemistry</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Delivery Systems</topic><topic>Gold - chemistry</topic><topic>Gold - pharmacology</topic><topic>Gold nanoparticles (AuNP)</topic><topic>Humans</topic><topic>KRAS mutant colorectal cancer</topic><topic>Metal Nanoparticles - chemistry</topic><topic>Mice, Nude</topic><topic>Mutation</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Tumor suppression</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hung, Wei-Hung</creatorcontrib><creatorcontrib>Zheng, Jia-Huei</creatorcontrib><creatorcontrib>Lee, Kuen-Chan</creatorcontrib><creatorcontrib>Cho, Er-Chieh</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hung, Wei-Hung</au><au>Zheng, Jia-Huei</au><au>Lee, Kuen-Chan</au><au>Cho, Er-Chieh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Doxorubicin conjugated AuNP/biopolymer composites facilitate cell cycle regulation and exhibit superior tumor suppression potential in KRAS mutant colorectal cancer</atitle><jtitle>Journal of biotechnology</jtitle><addtitle>J Biotechnol</addtitle><date>2019-12-20</date><risdate>2019</risdate><volume>306</volume><spage>149</spage><epage>158</epage><pages>149-158</pages><issn>0168-1656</issn><eissn>1873-4863</eissn><abstract>•AuNP/biopolymer therapeutic system with doxorubicin was designed and synthesized.•The system was characterized by UV spectrum, TEM, and zeta potential measurement.•Cancer cells were examined by MTT and cell cycle assays after the treatment.•Our system exhibits superior tumor suppression potential in the animal model. Colorectal cancer is a leading cause of death in the world. Despite the progress in therapeutic development, there are still challenges in clinical practice. Nanomedicine has emerged as a solution to enhance traditional therapy. Gold nanoparticles (AuNP) have been demonstrated as potential appliance in treating cancers, yet few studies investigated the capacity of biopolymer-conjugated AuNP in colon cancer as well as examined the system in both cancer cell line and animal models. In this study, we designed the AuNP/biopolymer composite therapeutic system with a chemotherapy agent, doxorubicin (DOX). Two composites with different drug load were applied (referred to as AuPPPyA and AuPPPyB). The composites were characterized by UV spectrum, transmission electron microscope (TEM), zeta potential measurement, and cell cycle analysis. Both therapeutic systems exhibited superior cytotoxic effects compared to DOX alone group. 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subjects Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biopolymer
Biopolymers - chemistry
Cell Cycle Checkpoints - drug effects
Cell cycle regulation
Cell Line, Tumor
Cell Survival - drug effects
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Delivery Systems
Gold - chemistry
Gold - pharmacology
Gold nanoparticles (AuNP)
Humans
KRAS mutant colorectal cancer
Metal Nanoparticles - chemistry
Mice, Nude
Mutation
Proto-Oncogene Proteins p21(ras) - genetics
Tumor suppression
Xenograft Model Antitumor Assays
title Doxorubicin conjugated AuNP/biopolymer composites facilitate cell cycle regulation and exhibit superior tumor suppression potential in KRAS mutant colorectal cancer
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