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 |
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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. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-6d99f34c4983fe17e56f8f1e4505a17698adf821e0e6f9dcc2276854b93722103</citedby><cites>FETCH-LOGICAL-c402t-6d99f34c4983fe17e56f8f1e4505a17698adf821e0e6f9dcc2276854b93722103</cites><orcidid>0000-0002-0921-4916 ; 0000-0002-4364-6034</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168165619308788$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31568802$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hung, Wei-Hung</creatorcontrib><creatorcontrib>Zheng, Jia-Huei</creatorcontrib><creatorcontrib>Lee, Kuen-Chan</creatorcontrib><creatorcontrib>Cho, Er-Chieh</creatorcontrib><title>Doxorubicin conjugated AuNP/biopolymer composites facilitate cell cycle regulation and exhibit superior tumor suppression potential in KRAS mutant colorectal cancer</title><title>Journal of biotechnology</title><addtitle>J Biotechnol</addtitle><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.</description><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biopolymer</subject><subject>Biopolymers - chemistry</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell cycle regulation</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Delivery Systems</subject><subject>Gold - chemistry</subject><subject>Gold - pharmacology</subject><subject>Gold nanoparticles (AuNP)</subject><subject>Humans</subject><subject>KRAS mutant colorectal cancer</subject><subject>Metal Nanoparticles - chemistry</subject><subject>Mice, Nude</subject><subject>Mutation</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Tumor suppression</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0168-1656</issn><issn>1873-4863</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuO1DAQRS0EYpqBTwB5ySY9thM79gq1ZniJESAea8txKoOjJA5-oOn_4UNx1A1bpJItq07VddVF6Dkle0qouBr3Y-d8ArtnhKo9KUH5A7Sjsq2rRor6IdoVTlZUcHGBnsQ4EkIaxeljdFFTLqQkbId-3_h7H3LnrFuw9cuY70yCHh_yx89XRWD103GGUFLz6qNLEPFgrJtcKhi2ME3YHu0EOMBdnkxyfsFm6THc_3CdSzjmFYLzAac8l7M81wAxbthafr8kZyZcpD98OXzFc05mSUVr8gFsKhlrFgvhKXo0mCnCs_N9ib6_ef3t-l11--nt--vDbWUbwlIleqWGurGNkvUAtAUuBjlQaDjhhrZCSdMPklEgIAbVW8tYKyRvOlW3jFFSX6KXp75r8D8zxKRnF7cZzQI-R82YUlsbRQvKT6gNPsYAg16Dm004akr0ZpAe9dkgvRmkSQnKS92Ls0TuZuj_Vf11pACvTgCUQX85CDpaB2ULvdt2onvv_iPxB4A0qNk</recordid><startdate>20191220</startdate><enddate>20191220</enddate><creator>Hung, Wei-Hung</creator><creator>Zheng, Jia-Huei</creator><creator>Lee, Kuen-Chan</creator><creator>Cho, Er-Chieh</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0921-4916</orcidid><orcidid>https://orcid.org/0000-0002-4364-6034</orcidid></search><sort><creationdate>20191220</creationdate><title>Doxorubicin conjugated AuNP/biopolymer composites facilitate cell cycle regulation and exhibit superior tumor suppression potential in KRAS mutant colorectal cancer</title><author>Hung, Wei-Hung ; 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. 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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31568802</pmid><doi>10.1016/j.jbiotec.2019.09.015</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0921-4916</orcidid><orcidid>https://orcid.org/0000-0002-4364-6034</orcidid></addata></record> |
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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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