A Multifunctional Peptide‐Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus
Gene therapy has immense potential as a therapeutic approach to serious diseases. However, efficient delivery and real‐time tracking of gene therapeutic agents have not been solved well for successful gene‐based therapeutics. Herein we present a versatile gene‐delivery strategy for efficient and vis...
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| Veröffentlicht in: | Angewandte Chemie 2019-04, Vol.131 (15), p.5103-5107 |
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| creator | Cheng, Yong Sun, Chunli Liu, Rui Yang, Juliang Dai, Jun Zhai, Tianyou Lou, Xiaoding Xia, Fan |
| description | Gene therapy has immense potential as a therapeutic approach to serious diseases. However, efficient delivery and real‐time tracking of gene therapeutic agents have not been solved well for successful gene‐based therapeutics. Herein we present a versatile gene‐delivery strategy for efficient and visualized delivery of therapeutic genes into the targeted nucleus. We developed an integrin‐targeted, cell‐permeable, and nucleocytoplasmic trafficking peptide‐conjugated AIEgen named TDNCP for the efficient and sequential targeted delivery of an antisense single‐stranded DNA oligonucleotide (ASO) and tracking of the delivery process into the nucleus. As compared with TDNCP/siRNA‐NPs (siRNA functions mainly in the cytoplasm), TDNCP/ASO‐NPs (ASO functions mainly in the nucleus) exhibited a better interference effect, which further indicates that TDNCP is a nucleus‐targeting vector. Moreover, TDNCP/ASO‐NPs showed a favorable tumor‐suppressive effect in vivo.
Verfolgen der Lieferung: Das Konjugat TNCP transportiert Gentherapeutika in den Kern von Krebszellen und ermöglicht deren Echtzeitverfolgung. TNCP besteht aus vier Segmenten: einem Target‐Peptid (Ligand für den Integrin‐αvβ3‐Rezeptor), einem Kernlokalisierungssignal, einem zelldurchdringenden Peptid und PyTPE, einem Molekül mit AIE‐Eigenschaften. Nanopartikel, die mit einem Antisense‐Oligonukleotid (ASO) gebildet wurden, zielen auf Krebszellen und unterdrücken das Tumorwachstum. |
| doi_str_mv | 10.1002/ange.201901527 |
| format | Article |
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Verfolgen der Lieferung: Das Konjugat TNCP transportiert Gentherapeutika in den Kern von Krebszellen und ermöglicht deren Echtzeitverfolgung. TNCP besteht aus vier Segmenten: einem Target‐Peptid (Ligand für den Integrin‐αvβ3‐Rezeptor), einem Kernlokalisierungssignal, einem zelldurchdringenden Peptid und PyTPE, einem Molekül mit AIE‐Eigenschaften. Nanopartikel, die mit einem Antisense‐Oligonukleotid (ASO) gebildet wurden, zielen auf Krebszellen und unterdrücken das Tumorwachstum.</description><identifier>ISSN: 0044-8249</identifier><identifier>EISSN: 1521-3757</identifier><identifier>DOI: 10.1002/ange.201901527</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>AIE-Luminogene ; Antisense DNA ; Antisense oligonucleotides ; Antisense-Oligonukleotide ; Chemical compounds ; Chemistry ; Cytoplasm ; Deoxyribonucleic acid ; DNA ; Gene therapy ; Gene transfer ; Gentransport ; Kern-Targeting ; Multifunktionelle Peptide ; Nuclei (cytology) ; Peptides ; Pharmacology ; siRNA ; Tracking</subject><ispartof>Angewandte Chemie, 2019-04, Vol.131 (15), p.5103-5107</ispartof><rights>2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1627-fa864cebdca831ecb1e8267085738a187153b9b97ebf617747407042c7e811c13</citedby><cites>FETCH-LOGICAL-c1627-fa864cebdca831ecb1e8267085738a187153b9b97ebf617747407042c7e811c13</cites><orcidid>0000-0001-7705-4638</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fange.201901527$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fange.201901527$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids></links><search><creatorcontrib>Cheng, Yong</creatorcontrib><creatorcontrib>Sun, Chunli</creatorcontrib><creatorcontrib>Liu, Rui</creatorcontrib><creatorcontrib>Yang, Juliang</creatorcontrib><creatorcontrib>Dai, Jun</creatorcontrib><creatorcontrib>Zhai, Tianyou</creatorcontrib><creatorcontrib>Lou, Xiaoding</creatorcontrib><creatorcontrib>Xia, Fan</creatorcontrib><title>A Multifunctional Peptide‐Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus</title><title>Angewandte Chemie</title><description>Gene therapy has immense potential as a therapeutic approach to serious diseases. However, efficient delivery and real‐time tracking of gene therapeutic agents have not been solved well for successful gene‐based therapeutics. Herein we present a versatile gene‐delivery strategy for efficient and visualized delivery of therapeutic genes into the targeted nucleus. We developed an integrin‐targeted, cell‐permeable, and nucleocytoplasmic trafficking peptide‐conjugated AIEgen named TDNCP for the efficient and sequential targeted delivery of an antisense single‐stranded DNA oligonucleotide (ASO) and tracking of the delivery process into the nucleus. As compared with TDNCP/siRNA‐NPs (siRNA functions mainly in the cytoplasm), TDNCP/ASO‐NPs (ASO functions mainly in the nucleus) exhibited a better interference effect, which further indicates that TDNCP is a nucleus‐targeting vector. Moreover, TDNCP/ASO‐NPs showed a favorable tumor‐suppressive effect in vivo.
Verfolgen der Lieferung: Das Konjugat TNCP transportiert Gentherapeutika in den Kern von Krebszellen und ermöglicht deren Echtzeitverfolgung. TNCP besteht aus vier Segmenten: einem Target‐Peptid (Ligand für den Integrin‐αvβ3‐Rezeptor), einem Kernlokalisierungssignal, einem zelldurchdringenden Peptid und PyTPE, einem Molekül mit AIE‐Eigenschaften. Nanopartikel, die mit einem Antisense‐Oligonukleotid (ASO) gebildet wurden, zielen auf Krebszellen und unterdrücken das Tumorwachstum.</description><subject>AIE-Luminogene</subject><subject>Antisense DNA</subject><subject>Antisense oligonucleotides</subject><subject>Antisense-Oligonukleotide</subject><subject>Chemical compounds</subject><subject>Chemistry</subject><subject>Cytoplasm</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Gentransport</subject><subject>Kern-Targeting</subject><subject>Multifunktionelle Peptide</subject><subject>Nuclei (cytology)</subject><subject>Peptides</subject><subject>Pharmacology</subject><subject>siRNA</subject><subject>Tracking</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkMtOwzAQRS0EEqWwZW2JdYrtPOwso1JKpfKQKGvLccbBVXCKk4C64xP4Rr4EV0WwZDWzOGd05yJ0TsmEEsIulathwgjNCU0ZP0CjMGgU85QfohEhSRIJluTH6KTr1oSQjPF8hHyBb4emt2ZwuretUw1-gE1vK_j6-Jy2bj3UqocKF4tZDQ6b1uOZMVZbcD1WrsKP8DqE3QZxpXwNO3gODvAVNPYN_BZb17e4fwZ8N-gGhu4UHRnVdHD2M8fo6Xq2mt5Ey_v5YlosI01DtsgokSUaykorEVPQJQXBMk5EymOhqOA0jcu8zDmUJqOcJzwhnCRMcxCUahqP0cX-7sa3IWPXy3U7-PBhJxnNszTlgieBmuwp7duu82DkxtsX5beSErnrVe56lb-9BiHfC--2ge0_tCzu5rM_9xudBX1Z</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Cheng, Yong</creator><creator>Sun, Chunli</creator><creator>Liu, Rui</creator><creator>Yang, Juliang</creator><creator>Dai, Jun</creator><creator>Zhai, Tianyou</creator><creator>Lou, Xiaoding</creator><creator>Xia, Fan</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0001-7705-4638</orcidid></search><sort><creationdate>20190401</creationdate><title>A Multifunctional Peptide‐Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus</title><author>Cheng, Yong ; Sun, Chunli ; Liu, Rui ; Yang, Juliang ; Dai, Jun ; Zhai, Tianyou ; Lou, Xiaoding ; Xia, Fan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1627-fa864cebdca831ecb1e8267085738a187153b9b97ebf617747407042c7e811c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>AIE-Luminogene</topic><topic>Antisense DNA</topic><topic>Antisense oligonucleotides</topic><topic>Antisense-Oligonukleotide</topic><topic>Chemical compounds</topic><topic>Chemistry</topic><topic>Cytoplasm</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Gene therapy</topic><topic>Gene transfer</topic><topic>Gentransport</topic><topic>Kern-Targeting</topic><topic>Multifunktionelle Peptide</topic><topic>Nuclei (cytology)</topic><topic>Peptides</topic><topic>Pharmacology</topic><topic>siRNA</topic><topic>Tracking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Yong</creatorcontrib><creatorcontrib>Sun, Chunli</creatorcontrib><creatorcontrib>Liu, Rui</creatorcontrib><creatorcontrib>Yang, Juliang</creatorcontrib><creatorcontrib>Dai, Jun</creatorcontrib><creatorcontrib>Zhai, Tianyou</creatorcontrib><creatorcontrib>Lou, Xiaoding</creatorcontrib><creatorcontrib>Xia, Fan</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Yong</au><au>Sun, Chunli</au><au>Liu, Rui</au><au>Yang, Juliang</au><au>Dai, Jun</au><au>Zhai, Tianyou</au><au>Lou, Xiaoding</au><au>Xia, Fan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Multifunctional Peptide‐Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus</atitle><jtitle>Angewandte Chemie</jtitle><date>2019-04-01</date><risdate>2019</risdate><volume>131</volume><issue>15</issue><spage>5103</spage><epage>5107</epage><pages>5103-5107</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>Gene therapy has immense potential as a therapeutic approach to serious diseases. However, efficient delivery and real‐time tracking of gene therapeutic agents have not been solved well for successful gene‐based therapeutics. Herein we present a versatile gene‐delivery strategy for efficient and visualized delivery of therapeutic genes into the targeted nucleus. We developed an integrin‐targeted, cell‐permeable, and nucleocytoplasmic trafficking peptide‐conjugated AIEgen named TDNCP for the efficient and sequential targeted delivery of an antisense single‐stranded DNA oligonucleotide (ASO) and tracking of the delivery process into the nucleus. As compared with TDNCP/siRNA‐NPs (siRNA functions mainly in the cytoplasm), TDNCP/ASO‐NPs (ASO functions mainly in the nucleus) exhibited a better interference effect, which further indicates that TDNCP is a nucleus‐targeting vector. Moreover, TDNCP/ASO‐NPs showed a favorable tumor‐suppressive effect in vivo.
Verfolgen der Lieferung: Das Konjugat TNCP transportiert Gentherapeutika in den Kern von Krebszellen und ermöglicht deren Echtzeitverfolgung. TNCP besteht aus vier Segmenten: einem Target‐Peptid (Ligand für den Integrin‐αvβ3‐Rezeptor), einem Kernlokalisierungssignal, einem zelldurchdringenden Peptid und PyTPE, einem Molekül mit AIE‐Eigenschaften. Nanopartikel, die mit einem Antisense‐Oligonukleotid (ASO) gebildet wurden, zielen auf Krebszellen und unterdrücken das Tumorwachstum.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ange.201901527</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-7705-4638</orcidid></addata></record> |
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| subjects | AIE-Luminogene Antisense DNA Antisense oligonucleotides Antisense-Oligonukleotide Chemical compounds Chemistry Cytoplasm Deoxyribonucleic acid DNA Gene therapy Gene transfer Gentransport Kern-Targeting Multifunktionelle Peptide Nuclei (cytology) Peptides Pharmacology siRNA Tracking |
| title | A Multifunctional Peptide‐Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus |
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