Biodegradable thermosensitive hydrogel for SAHA and DDP delivery: therapeutic effects on oral squamous cell carcinoma xenografts
OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts....
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| Veröffentlicht in: | PloS one 2012-04, Vol.7 (4), p.e33860 |
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| creator | Li, Jing Gong, Changyang Feng, Xiaodong Zhou, Xikun Xu, Xiaoping Xie, Liang Wang, Ruinan Zhang, Dunfang Wang, Hui Deng, Peng Zhou, Min Ji, Ning Zhou, Yu Wang, Yun Wang, Zhiyong Liao, Ga Geng, Ning Chu, Liangyin Qian, Zhiyong Wang, Zhi Chen, Qianming |
| description | OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts.
The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts.
A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumor-beared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis.
The hydrogel system was a free-flowing sol at 10 °C, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and could improved therapeutic effects compared with a simple additive therapeutic effect of SAHA and DDP on mouse model.
Our research indicated that the novel SAHA-DDP/PECE system based on biodegradable PECE copolymer enhanced the therapeutic effects and could diminished the side effects of SAHA/DDP. The present work might be of great importance to the further exploration of the potential application of SAHA/DDP-hydrogel controlled drug release system in the treatment of OSCC. |
| doi_str_mv | 10.1371/journal.pone.0033860 |
| format | Article |
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The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts.
A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumor-beared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis.
The hydrogel system was a free-flowing sol at 10 °C, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and could improved therapeutic effects compared with a simple additive therapeutic effect of SAHA and DDP on mouse model.
Our research indicated that the novel SAHA-DDP/PECE system based on biodegradable PECE copolymer enhanced the therapeutic effects and could diminished the side effects of SAHA/DDP. The present work might be of great importance to the further exploration of the potential application of SAHA/DDP-hydrogel controlled drug release system in the treatment of OSCC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0033860</identifier><identifier>PMID: 22529899</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Apoptosis ; Apoptosis - drug effects ; Biodegradability ; Biodegradation ; Biology ; Body temperature ; Cancer therapies ; Carcinoma, Squamous Cell - blood supply ; Carcinoma, Squamous Cell - drug therapy ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Chemotherapy ; Controlled release ; Copolymers ; Cytotoxicity ; Delayed-Action Preparations ; Delivery scheduling ; Desertification ; Drug delivery ; Drug Delivery Systems ; Endoplasmic reticulum ; Female ; Health aspects ; Histone Deacetylase Inhibitors - administration & dosage ; Hydrogels ; Hydrogels - chemical synthesis ; Hydrogels - chemistry ; Hydrogels - toxicity ; Hydroxamic Acids - administration & dosage ; Immunohistochemistry ; Laboratory animals ; Lung cancer ; Materials Science ; Medicine ; Mice ; Mice, Nude ; Mouth Neoplasms - blood supply ; Mouth Neoplasms - drug therapy ; Nanoparticles ; Neovascularization, Pathologic - drug therapy ; Oncology ; Oral cancer ; Oral diseases ; Oral squamous cell carcinoma ; Physiology ; Polymers - chemical synthesis ; Polymers - therapeutic use ; Polymers - toxicity ; Side effects ; Squamous cell carcinoma ; Sustained release ; Thermosensitive ; Tumors ; Vorinostat ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>PloS one, 2012-04, Vol.7 (4), p.e33860</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Li et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c622t-9d7b646e6b6fc05d990ca76148c8dbae11f98827d216a008e872827ec66da27d3</citedby><cites>FETCH-LOGICAL-c622t-9d7b646e6b6fc05d990ca76148c8dbae11f98827d216a008e872827ec66da27d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329521/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329521/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22529899$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Xie, Jingwu</contributor><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Gong, Changyang</creatorcontrib><creatorcontrib>Feng, Xiaodong</creatorcontrib><creatorcontrib>Zhou, Xikun</creatorcontrib><creatorcontrib>Xu, Xiaoping</creatorcontrib><creatorcontrib>Xie, Liang</creatorcontrib><creatorcontrib>Wang, Ruinan</creatorcontrib><creatorcontrib>Zhang, Dunfang</creatorcontrib><creatorcontrib>Wang, Hui</creatorcontrib><creatorcontrib>Deng, Peng</creatorcontrib><creatorcontrib>Zhou, Min</creatorcontrib><creatorcontrib>Ji, Ning</creatorcontrib><creatorcontrib>Zhou, Yu</creatorcontrib><creatorcontrib>Wang, Yun</creatorcontrib><creatorcontrib>Wang, Zhiyong</creatorcontrib><creatorcontrib>Liao, Ga</creatorcontrib><creatorcontrib>Geng, Ning</creatorcontrib><creatorcontrib>Chu, Liangyin</creatorcontrib><creatorcontrib>Qian, Zhiyong</creatorcontrib><creatorcontrib>Wang, Zhi</creatorcontrib><creatorcontrib>Chen, Qianming</creatorcontrib><title>Biodegradable thermosensitive hydrogel for SAHA and DDP delivery: therapeutic effects on oral squamous cell carcinoma xenografts</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts.
The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts.
A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumor-beared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis.
The hydrogel system was a free-flowing sol at 10 °C, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and could improved therapeutic effects compared with a simple additive therapeutic effect of SAHA and DDP on mouse model.
Our research indicated that the novel SAHA-DDP/PECE system based on biodegradable PECE copolymer enhanced the therapeutic effects and could diminished the side effects of SAHA/DDP. The present work might be of great importance to the further exploration of the potential application of SAHA/DDP-hydrogel controlled drug release system in the treatment of OSCC.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biodegradability</subject><subject>Biodegradation</subject><subject>Biology</subject><subject>Body temperature</subject><subject>Cancer therapies</subject><subject>Carcinoma, Squamous Cell - blood supply</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotherapy</subject><subject>Controlled release</subject><subject>Copolymers</subject><subject>Cytotoxicity</subject><subject>Delayed-Action Preparations</subject><subject>Delivery scheduling</subject><subject>Desertification</subject><subject>Drug delivery</subject><subject>Drug Delivery Systems</subject><subject>Endoplasmic reticulum</subject><subject>Female</subject><subject>Health aspects</subject><subject>Histone Deacetylase Inhibitors - administration & dosage</subject><subject>Hydrogels</subject><subject>Hydrogels - chemical synthesis</subject><subject>Hydrogels - chemistry</subject><subject>Hydrogels - toxicity</subject><subject>Hydroxamic Acids - administration & dosage</subject><subject>Immunohistochemistry</subject><subject>Laboratory animals</subject><subject>Lung cancer</subject><subject>Materials Science</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mouth Neoplasms - blood supply</subject><subject>Mouth Neoplasms - drug therapy</subject><subject>Nanoparticles</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Oncology</subject><subject>Oral cancer</subject><subject>Oral diseases</subject><subject>Oral squamous cell carcinoma</subject><subject>Physiology</subject><subject>Polymers - chemical synthesis</subject><subject>Polymers - therapeutic use</subject><subject>Polymers - toxicity</subject><subject>Side effects</subject><subject>Squamous cell carcinoma</subject><subject>Sustained release</subject><subject>Thermosensitive</subject><subject>Tumors</subject><subject>Vorinostat</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNku9r1DAcxosobk7_A9GAIPjizvxo09YXwrmpOxhMnPo2pMk3vYy0uSXt2L3zTzfbdeMOFKQv2n7zeZ4kD0-WvSR4TlhJ3l_6MfTSzde-hznGjFUcP8oOSc3ojFPMHu98H2TPYrzEuEgQf5odUFrQuqrrw-z3J-s1tEFq2ThAwwpC5yP00Q72GtBqo4NvwSHjA7pYnC6Q7DU6OfmGNLgEhM2HO41cwzhYhcAYUENEvkc-SIfi1Sg7P0akwDmkZFC2951EN9D7tKkZ4vPsiZEuwovpfZT9_PL5x_Hp7Oz86_J4cTZTnNJhVuuy4TkH3nCjcKHrGitZcpJXqtKNBEJMXVW01JRwiXEFVUnTLyjOtUxjdpS93vqunY9iCi8KwmheFBUp8kQst4T28lKsg-1k2Agvrbgb-NAKGdIlHYiSMExYXjeVNHlTGak5zXOmm6bOCTMqeX2cdhubDrSCfkhx7Jnur_R2JVp_LRijdUFJMngzGQR_NUIc_nHkiWplOpXtjU9mqrNRiUVelrjMOS0SNf8LlR4NnVWpPsam-Z7g3Z4gMQPcDK0cYxTLi-__z57_2mff7rArkG5YRe9Sc3wf98F8C6rgYwxgHpIjWNy2_z4Ncdt-MbU_yV7tpv4guq87-wOpjQE9</recordid><startdate>20120418</startdate><enddate>20120418</enddate><creator>Li, 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(purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central 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Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Jing</au><au>Gong, Changyang</au><au>Feng, Xiaodong</au><au>Zhou, Xikun</au><au>Xu, Xiaoping</au><au>Xie, Liang</au><au>Wang, Ruinan</au><au>Zhang, Dunfang</au><au>Wang, Hui</au><au>Deng, Peng</au><au>Zhou, Min</au><au>Ji, Ning</au><au>Zhou, Yu</au><au>Wang, Yun</au><au>Wang, Zhiyong</au><au>Liao, Ga</au><au>Geng, Ning</au><au>Chu, Liangyin</au><au>Qian, Zhiyong</au><au>Wang, Zhi</au><au>Chen, Qianming</au><au>Xie, Jingwu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biodegradable thermosensitive hydrogel for SAHA and DDP delivery: therapeutic effects on oral squamous cell carcinoma xenografts</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-04-18</date><risdate>2012</risdate><volume>7</volume><issue>4</issue><spage>e33860</spage><pages>e33860-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts.
The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts.
A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumor-beared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis.
The hydrogel system was a free-flowing sol at 10 °C, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and could improved therapeutic effects compared with a simple additive therapeutic effect of SAHA and DDP on mouse model.
Our research indicated that the novel SAHA-DDP/PECE system based on biodegradable PECE copolymer enhanced the therapeutic effects and could diminished the side effects of SAHA/DDP. The present work might be of great importance to the further exploration of the potential application of SAHA/DDP-hydrogel controlled drug release system in the treatment of OSCC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22529899</pmid><doi>10.1371/journal.pone.0033860</doi><tpages>e33860</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-04, Vol.7 (4), p.e33860 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1324558154 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Animals Antineoplastic Combined Chemotherapy Protocols - administration & dosage Apoptosis Apoptosis - drug effects Biodegradability Biodegradation Biology Body temperature Cancer therapies Carcinoma, Squamous Cell - blood supply Carcinoma, Squamous Cell - drug therapy Cell Line, Tumor Cell Proliferation - drug effects Chemotherapy Controlled release Copolymers Cytotoxicity Delayed-Action Preparations Delivery scheduling Desertification Drug delivery Drug Delivery Systems Endoplasmic reticulum Female Health aspects Histone Deacetylase Inhibitors - administration & dosage Hydrogels Hydrogels - chemical synthesis Hydrogels - chemistry Hydrogels - toxicity Hydroxamic Acids - administration & dosage Immunohistochemistry Laboratory animals Lung cancer Materials Science Medicine Mice Mice, Nude Mouth Neoplasms - blood supply Mouth Neoplasms - drug therapy Nanoparticles Neovascularization, Pathologic - drug therapy Oncology Oral cancer Oral diseases Oral squamous cell carcinoma Physiology Polymers - chemical synthesis Polymers - therapeutic use Polymers - toxicity Side effects Squamous cell carcinoma Sustained release Thermosensitive Tumors Vorinostat Xenograft Model Antitumor Assays Xenografts |
| title | Biodegradable thermosensitive hydrogel for SAHA and DDP delivery: therapeutic effects on oral squamous cell carcinoma xenografts |
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