Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid-siRNA in pancreatic tumors
The major barrier for using small interfering RNA (siRNA) as cancer therapeutics is the inadequate delivery and transfection in solid tumors. We have previously shown that paclitaxel tumor priming, by inducing apoptosis, expands the tumor interstitial space, improves the penetration and dispersion o...
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| Veröffentlicht in: | Journal of controlled release 2015-10, Vol.216, p.103-110 |
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| creator | Wang, Jie Lu, Ze Wang, Junfeng Cui, Minjian Yeung, Bertrand Z. Cole, David J. Wientjes, M. Guillaume Au, Jessie L.-S. |
| description | The major barrier for using small interfering RNA (siRNA) as cancer therapeutics is the inadequate delivery and transfection in solid tumors. We have previously shown that paclitaxel tumor priming, by inducing apoptosis, expands the tumor interstitial space, improves the penetration and dispersion of nanoparticles and siRNA-lipoplexes in 3-dimensional tumor histocultures, and promotes the delivery and transfection efficiency of siRNA-lipoplexes under the locoregional setting in vivo (i.e., intraperitoneal treatment of intraperitoneal tumors). The current study evaluated whether tumor priming is functional for systemically delivered siRNA via intravenous injection, which would subject siRNA to several additional delivery barriers and elimination processes. We used the same pegylated cationic (PCat)-siRNA lipoplexes as in the intraperitoneal study to treat mice bearing subcutaneous human pancreatic Hs766T xenograft tumors. The target gene was survivin, an inducible chemoresistance gene. The results show single agent paclitaxel delayed tumor growth but also significantly induced the survivin protein level in residual tumors, whereas addition of PCat-siSurvivin completely reversed the paclitaxel-induced survivin and enhanced the paclitaxel activity (p |
| doi_str_mv | 10.1016/j.jconrel.2015.08.012 |
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[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2015.08.012</identifier><identifier>PMID: 26272765</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - administration & dosage ; Antineoplastic Agents, Phytogenic - pharmacology ; Cell Line, Tumor ; Chemo-gene therapy ; Drug Delivery Systems ; Drug Resistance, Neoplasm ; Female ; Gene Silencing - drug effects ; Genetic Therapy - methods ; Humans ; Inhibitor of Apoptosis Proteins - drug effects ; Injections, Intravenous ; Intravenous siRNA delivery ; Lipids - chemistry ; Mice ; Mice, Nude ; Paclitaxel ; Paclitaxel - administration & dosage ; Paclitaxel - pharmacology ; Pancreatic cancer ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - therapy ; Peritoneal Neoplasms - drug therapy ; RNA, Neoplasm - metabolism ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - pharmacology ; Survivin ; Transfection ; Xenograft Model Antitumor Assays</subject><ispartof>Journal of controlled release, 2015-10, Vol.216, p.103-110</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-6281e9855dc2a925a52aec8328d0c06ffa3e1c01eacd1f7486a09098c8dd835a3</citedby><cites>FETCH-LOGICAL-c467t-6281e9855dc2a925a52aec8328d0c06ffa3e1c01eacd1f7486a09098c8dd835a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jconrel.2015.08.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26272765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Lu, Ze</creatorcontrib><creatorcontrib>Wang, Junfeng</creatorcontrib><creatorcontrib>Cui, Minjian</creatorcontrib><creatorcontrib>Yeung, Bertrand Z.</creatorcontrib><creatorcontrib>Cole, David J.</creatorcontrib><creatorcontrib>Wientjes, M. Guillaume</creatorcontrib><creatorcontrib>Au, Jessie L.-S.</creatorcontrib><title>Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid-siRNA in pancreatic tumors</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>The major barrier for using small interfering RNA (siRNA) as cancer therapeutics is the inadequate delivery and transfection in solid tumors. We have previously shown that paclitaxel tumor priming, by inducing apoptosis, expands the tumor interstitial space, improves the penetration and dispersion of nanoparticles and siRNA-lipoplexes in 3-dimensional tumor histocultures, and promotes the delivery and transfection efficiency of siRNA-lipoplexes under the locoregional setting in vivo (i.e., intraperitoneal treatment of intraperitoneal tumors). The current study evaluated whether tumor priming is functional for systemically delivered siRNA via intravenous injection, which would subject siRNA to several additional delivery barriers and elimination processes. We used the same pegylated cationic (PCat)-siRNA lipoplexes as in the intraperitoneal study to treat mice bearing subcutaneous human pancreatic Hs766T xenograft tumors. The target gene was survivin, an inducible chemoresistance gene. The results show single agent paclitaxel delayed tumor growth but also significantly induced the survivin protein level in residual tumors, whereas addition of PCat-siSurvivin completely reversed the paclitaxel-induced survivin and enhanced the paclitaxel activity (p<0.05). In comparison, PCat-siSurvivin alone did not yield survivin knockdown or antitumor activity, indicating the in vivo effectiveness of intravenous siRNA-mediated gene silencing requires paclitaxel cotreatment. Additional in vitro studies showed that paclitaxel promoted the cytoplasmic release of siGLO, a 22 nucleotide double-stranded RNA that has no mRNA targets, from its PCat lipoplex and/or endosomes/lysosomes. Taken together, our earlier and current data show paclitaxel tumor priming, by promoting the interstitial transport and cytoplasmic release, is critical to promote the delivery and transfection of siRNA in vivo. In addition, because paclitaxel has broad spectrum activity and is used to treat multiple types of solid tumors including the hard-to-treat pancreatic cancer, the synergistic paclitaxel+siSurvivin combination represents a potentially useful chemo-gene therapy.
[Display omitted]</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - administration & dosage</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Chemo-gene therapy</subject><subject>Drug Delivery Systems</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Gene Silencing - drug effects</subject><subject>Genetic Therapy - methods</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins - drug effects</subject><subject>Injections, Intravenous</subject><subject>Intravenous siRNA delivery</subject><subject>Lipids - chemistry</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Paclitaxel</subject><subject>Paclitaxel - administration & dosage</subject><subject>Paclitaxel - pharmacology</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>Peritoneal Neoplasms - drug therapy</subject><subject>RNA, Neoplasm - metabolism</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Survivin</subject><subject>Transfection</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctuFDEQRS0EIpPAJ4B6yaYbP9qvDSiKgCBFgBCsLWNXBw9ue7B7RuTvcWuGCFasSqo6detxEXpG8EAwES-3w9blVCAOFBM-YDVgQh-gDVGS9aPW_CHaNE71THB9hs5r3WKMORvlY3RGBZVUCr5BPz5ZF8Nif0Hslv2cS7crYQ7ptsU85wVq5yGGA5S7zibfLcWmOoFbQk5dnrqQWuYAKe9rF8Mu-L6Gzx8uW77b2eQK2CW4o3J9gh5NNlZ4eooX6OvbN1-urvubj-_eX13e9G4UcukFVQS04tw7ajXlllMLTjGqPHZYTJNlQBwmYJ0nkxyVsFhjrZzyXjFu2QV6ddTd7b_N4B2sO0azHmbLnck2mH8rKXw3t_lgRq6oHlkTeHESKPnnHupi5lAdxGgTtEMNkURoJiVbUX5EXcm1FpjuxxBsVqPM1pyMMqtRBivTjGp9z__e8b7rjzMNeH0EoH3qEKCY6gIkBz6U9n7jc_jPiN_ozKtF</recordid><startdate>20151028</startdate><enddate>20151028</enddate><creator>Wang, Jie</creator><creator>Lu, Ze</creator><creator>Wang, Junfeng</creator><creator>Cui, Minjian</creator><creator>Yeung, Bertrand Z.</creator><creator>Cole, David J.</creator><creator>Wientjes, M. Guillaume</creator><creator>Au, Jessie L.-S.</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><scope>5PM</scope></search><sort><creationdate>20151028</creationdate><title>Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid-siRNA in pancreatic tumors</title><author>Wang, Jie ; Lu, Ze ; Wang, Junfeng ; Cui, Minjian ; Yeung, Bertrand Z. ; Cole, David J. ; Wientjes, M. Guillaume ; Au, Jessie L.-S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-6281e9855dc2a925a52aec8328d0c06ffa3e1c01eacd1f7486a09098c8dd835a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - administration & dosage</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Chemo-gene therapy</topic><topic>Drug Delivery Systems</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Gene Silencing - drug effects</topic><topic>Genetic Therapy - methods</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins - drug effects</topic><topic>Injections, Intravenous</topic><topic>Intravenous siRNA delivery</topic><topic>Lipids - chemistry</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Paclitaxel</topic><topic>Paclitaxel - administration & dosage</topic><topic>Paclitaxel - pharmacology</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - therapy</topic><topic>Peritoneal Neoplasms - drug therapy</topic><topic>RNA, Neoplasm - metabolism</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Survivin</topic><topic>Transfection</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Lu, Ze</creatorcontrib><creatorcontrib>Wang, Junfeng</creatorcontrib><creatorcontrib>Cui, Minjian</creatorcontrib><creatorcontrib>Yeung, Bertrand Z.</creatorcontrib><creatorcontrib>Cole, David J.</creatorcontrib><creatorcontrib>Wientjes, M. Guillaume</creatorcontrib><creatorcontrib>Au, Jessie L.-S.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jie</au><au>Lu, Ze</au><au>Wang, Junfeng</au><au>Cui, Minjian</au><au>Yeung, Bertrand Z.</au><au>Cole, David J.</au><au>Wientjes, M. Guillaume</au><au>Au, Jessie L.-S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid-siRNA in pancreatic tumors</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2015-10-28</date><risdate>2015</risdate><volume>216</volume><spage>103</spage><epage>110</epage><pages>103-110</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>The major barrier for using small interfering RNA (siRNA) as cancer therapeutics is the inadequate delivery and transfection in solid tumors. We have previously shown that paclitaxel tumor priming, by inducing apoptosis, expands the tumor interstitial space, improves the penetration and dispersion of nanoparticles and siRNA-lipoplexes in 3-dimensional tumor histocultures, and promotes the delivery and transfection efficiency of siRNA-lipoplexes under the locoregional setting in vivo (i.e., intraperitoneal treatment of intraperitoneal tumors). The current study evaluated whether tumor priming is functional for systemically delivered siRNA via intravenous injection, which would subject siRNA to several additional delivery barriers and elimination processes. We used the same pegylated cationic (PCat)-siRNA lipoplexes as in the intraperitoneal study to treat mice bearing subcutaneous human pancreatic Hs766T xenograft tumors. The target gene was survivin, an inducible chemoresistance gene. The results show single agent paclitaxel delayed tumor growth but also significantly induced the survivin protein level in residual tumors, whereas addition of PCat-siSurvivin completely reversed the paclitaxel-induced survivin and enhanced the paclitaxel activity (p<0.05). In comparison, PCat-siSurvivin alone did not yield survivin knockdown or antitumor activity, indicating the in vivo effectiveness of intravenous siRNA-mediated gene silencing requires paclitaxel cotreatment. Additional in vitro studies showed that paclitaxel promoted the cytoplasmic release of siGLO, a 22 nucleotide double-stranded RNA that has no mRNA targets, from its PCat lipoplex and/or endosomes/lysosomes. Taken together, our earlier and current data show paclitaxel tumor priming, by promoting the interstitial transport and cytoplasmic release, is critical to promote the delivery and transfection of siRNA in vivo. In addition, because paclitaxel has broad spectrum activity and is used to treat multiple types of solid tumors including the hard-to-treat pancreatic cancer, the synergistic paclitaxel+siSurvivin combination represents a potentially useful chemo-gene therapy.
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| subjects | Animals Antineoplastic Agents, Phytogenic - administration & dosage Antineoplastic Agents, Phytogenic - pharmacology Cell Line, Tumor Chemo-gene therapy Drug Delivery Systems Drug Resistance, Neoplasm Female Gene Silencing - drug effects Genetic Therapy - methods Humans Inhibitor of Apoptosis Proteins - drug effects Injections, Intravenous Intravenous siRNA delivery Lipids - chemistry Mice Mice, Nude Paclitaxel Paclitaxel - administration & dosage Paclitaxel - pharmacology Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - therapy Peritoneal Neoplasms - drug therapy RNA, Neoplasm - metabolism RNA, Small Interfering - administration & dosage RNA, Small Interfering - pharmacology Survivin Transfection Xenograft Model Antitumor Assays |
| title | Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid-siRNA in pancreatic tumors |
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