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Environment-stimulated nanocarriers enabling multi-active sites for high drug encapsulation as an "on demand" drug release system
Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensiti...
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| Published in: | Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2018-04, Vol.6 (15), p.2258-2273 |
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| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c337t-a678a26964d65277689e9c310907a1e88ea00fb9770b25c90127abcacf3eef023 |
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| cites | cdi_FETCH-LOGICAL-c337t-a678a26964d65277689e9c310907a1e88ea00fb9770b25c90127abcacf3eef023 |
| container_end_page | 2273 |
| container_issue | 15 |
| container_start_page | 2258 |
| container_title | Journal of materials chemistry. B, Materials for biology and medicine |
| container_volume | 6 |
| creator | Cheng, F. R Su, T Cao, J Luo, X. L Li, Li Pu, Yuji He, B |
| description | Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensitive polyethylene glycol and imidazole to construct bioreducible nanocarriers (PLM-
g
-ss-EGA). The uniform spherical shape and high stability of the PLM-
g
-ss-EGA nanocarriers were demonstrated by dynamic light scattering (DLS) and dissipative particle dynamics (DPD) simulations. Enhanced interaction between the monomers in this novel nanocarrier doubled its drug loading efficiency (15%) as compared to that of traditional polyester nanocarriers (5-7%). Moreover, stimulus-responsive assessment and
in vitro
drug release studies showed that these bioreducible nanocarriers can balance extracellular stability in blood circulation and intracellular "on demand" release.
In vitro
and
in vivo
assays have demonstrated that these bioreducible nanocarriers not only can substantially enhance antitumor efficacy as compared to insensitive micelles and even comparably to free DOX·HCl, but can also greatly reduce unwanted side effects in other organs. The encouraging anticancer efficiency of these poly(malic acid)-based nanocarriers opens a new avenue to design multifunctional biodegradable polyester drug-delivery systems.
Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. |
| doi_str_mv | 10.1039/c8tb00132d |
| format | article |
| fullrecord | <record><control><sourceid>proquest_rsc_p</sourceid><recordid>TN_cdi_rsc_primary_c8tb00132d</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2387254618</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-a678a26964d65277689e9c310907a1e88ea00fb9770b25c90127abcacf3eef023</originalsourceid><addsrcrecordid>eNpd0cFrFDEUBvAgFltqL96VUC9FmPqS7CSZo65VC4VeKngb3mTebFNmMmuSKfTof27arSuYSx68Hx8hH2NvBJwLUM1HZ3MHIJTsX7AjCTVUphb25X6Gn4fsJKU7KMcKbdXqFTtUUtarWusj9vsi3Ps4h4lCrlL20zJipp4HDLPDGD3FxClgN_qw4WWbfYUu-3viyWdKfJgjv_WbW97HZVOkw216zPBz4Jg4Bn5app4mDP3pDkUaCVMJeEiZptfsYMAx0cnzfcx-fL24WX-vrq6_Xa4_XVVOKZMr1Mai1I1e9bqWxmjbUOOUgAYMCrKWEGDoGmOgk7VrQEiDnUM3KKIBpDpmZ7vcbZx_LZRyO_nkaBwx0LykVipryq9oYQt9_x-9m5cYyutaCVKvrDJCF_Vhp1ycU4o0tNvoJ4wPrYD2sZt2bW8-P3XzpeB3z5FLN1G_p3-bKODtDsTk9tt_5ao_geyUJA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2026483716</pqid></control><display><type>article</type><title>Environment-stimulated nanocarriers enabling multi-active sites for high drug encapsulation as an "on demand" drug release system</title><source>Royal Society of Chemistry</source><creator>Cheng, F. R ; Su, T ; Cao, J ; Luo, X. L ; Li, Li ; Pu, Yuji ; He, B</creator><creatorcontrib>Cheng, F. R ; Su, T ; Cao, J ; Luo, X. L ; Li, Li ; Pu, Yuji ; He, B</creatorcontrib><description>Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensitive polyethylene glycol and imidazole to construct bioreducible nanocarriers (PLM-
g
-ss-EGA). The uniform spherical shape and high stability of the PLM-
g
-ss-EGA nanocarriers were demonstrated by dynamic light scattering (DLS) and dissipative particle dynamics (DPD) simulations. Enhanced interaction between the monomers in this novel nanocarrier doubled its drug loading efficiency (15%) as compared to that of traditional polyester nanocarriers (5-7%). Moreover, stimulus-responsive assessment and
in vitro
drug release studies showed that these bioreducible nanocarriers can balance extracellular stability in blood circulation and intracellular "on demand" release.
In vitro
and
in vivo
assays have demonstrated that these bioreducible nanocarriers not only can substantially enhance antitumor efficacy as compared to insensitive micelles and even comparably to free DOX·HCl, but can also greatly reduce unwanted side effects in other organs. The encouraging anticancer efficiency of these poly(malic acid)-based nanocarriers opens a new avenue to design multifunctional biodegradable polyester drug-delivery systems.
Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications.</description><identifier>ISSN: 2050-750X</identifier><identifier>EISSN: 2050-7518</identifier><identifier>DOI: 10.1039/c8tb00132d</identifier><identifier>PMID: 32254566</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Anticancer properties ; Antitumor activity ; Biodegradability ; Biodegradation ; Blood circulation ; Drug delivery systems ; Drug development ; Dynamic stability ; Fabrication ; Imidazole ; Intracellular ; Light scattering ; Monomers ; Organs ; Photon correlation spectroscopy ; Polyester resins ; Polyesters ; Polyethylene glycol ; Polymalic acid ; Side effects ; Therapeutic applications</subject><ispartof>Journal of materials chemistry. B, Materials for biology and medicine, 2018-04, Vol.6 (15), p.2258-2273</ispartof><rights>Copyright Royal Society of Chemistry 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-a678a26964d65277689e9c310907a1e88ea00fb9770b25c90127abcacf3eef023</citedby><cites>FETCH-LOGICAL-c337t-a678a26964d65277689e9c310907a1e88ea00fb9770b25c90127abcacf3eef023</cites><orcidid>0000-0002-5591-2299 ; 0000-0003-3041-3933</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32254566$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, F. R</creatorcontrib><creatorcontrib>Su, T</creatorcontrib><creatorcontrib>Cao, J</creatorcontrib><creatorcontrib>Luo, X. L</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Pu, Yuji</creatorcontrib><creatorcontrib>He, B</creatorcontrib><title>Environment-stimulated nanocarriers enabling multi-active sites for high drug encapsulation as an "on demand" drug release system</title><title>Journal of materials chemistry. B, Materials for biology and medicine</title><addtitle>J Mater Chem B</addtitle><description>Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensitive polyethylene glycol and imidazole to construct bioreducible nanocarriers (PLM-
g
-ss-EGA). The uniform spherical shape and high stability of the PLM-
g
-ss-EGA nanocarriers were demonstrated by dynamic light scattering (DLS) and dissipative particle dynamics (DPD) simulations. Enhanced interaction between the monomers in this novel nanocarrier doubled its drug loading efficiency (15%) as compared to that of traditional polyester nanocarriers (5-7%). Moreover, stimulus-responsive assessment and
in vitro
drug release studies showed that these bioreducible nanocarriers can balance extracellular stability in blood circulation and intracellular "on demand" release.
In vitro
and
in vivo
assays have demonstrated that these bioreducible nanocarriers not only can substantially enhance antitumor efficacy as compared to insensitive micelles and even comparably to free DOX·HCl, but can also greatly reduce unwanted side effects in other organs. The encouraging anticancer efficiency of these poly(malic acid)-based nanocarriers opens a new avenue to design multifunctional biodegradable polyester drug-delivery systems.
Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications.</description><subject>Anticancer properties</subject><subject>Antitumor activity</subject><subject>Biodegradability</subject><subject>Biodegradation</subject><subject>Blood circulation</subject><subject>Drug delivery systems</subject><subject>Drug development</subject><subject>Dynamic stability</subject><subject>Fabrication</subject><subject>Imidazole</subject><subject>Intracellular</subject><subject>Light scattering</subject><subject>Monomers</subject><subject>Organs</subject><subject>Photon correlation spectroscopy</subject><subject>Polyester resins</subject><subject>Polyesters</subject><subject>Polyethylene glycol</subject><subject>Polymalic acid</subject><subject>Side effects</subject><subject>Therapeutic applications</subject><issn>2050-750X</issn><issn>2050-7518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpd0cFrFDEUBvAgFltqL96VUC9FmPqS7CSZo65VC4VeKngb3mTebFNmMmuSKfTof27arSuYSx68Hx8hH2NvBJwLUM1HZ3MHIJTsX7AjCTVUphb25X6Gn4fsJKU7KMcKbdXqFTtUUtarWusj9vsi3Ps4h4lCrlL20zJipp4HDLPDGD3FxClgN_qw4WWbfYUu-3viyWdKfJgjv_WbW97HZVOkw216zPBz4Jg4Bn5app4mDP3pDkUaCVMJeEiZptfsYMAx0cnzfcx-fL24WX-vrq6_Xa4_XVVOKZMr1Mai1I1e9bqWxmjbUOOUgAYMCrKWEGDoGmOgk7VrQEiDnUM3KKIBpDpmZ7vcbZx_LZRyO_nkaBwx0LykVipryq9oYQt9_x-9m5cYyutaCVKvrDJCF_Vhp1ycU4o0tNvoJ4wPrYD2sZt2bW8-P3XzpeB3z5FLN1G_p3-bKODtDsTk9tt_5ao_geyUJA</recordid><startdate>20180421</startdate><enddate>20180421</enddate><creator>Cheng, F. R</creator><creator>Su, T</creator><creator>Cao, J</creator><creator>Luo, X. 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L ; Li, Li ; Pu, Yuji ; He, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-a678a26964d65277689e9c310907a1e88ea00fb9770b25c90127abcacf3eef023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Anticancer properties</topic><topic>Antitumor activity</topic><topic>Biodegradability</topic><topic>Biodegradation</topic><topic>Blood circulation</topic><topic>Drug delivery systems</topic><topic>Drug development</topic><topic>Dynamic stability</topic><topic>Fabrication</topic><topic>Imidazole</topic><topic>Intracellular</topic><topic>Light scattering</topic><topic>Monomers</topic><topic>Organs</topic><topic>Photon correlation spectroscopy</topic><topic>Polyester resins</topic><topic>Polyesters</topic><topic>Polyethylene glycol</topic><topic>Polymalic acid</topic><topic>Side effects</topic><topic>Therapeutic applications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, F. R</creatorcontrib><creatorcontrib>Su, T</creatorcontrib><creatorcontrib>Cao, J</creatorcontrib><creatorcontrib>Luo, X. 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B, Materials for biology and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, F. R</au><au>Su, T</au><au>Cao, J</au><au>Luo, X. L</au><au>Li, Li</au><au>Pu, Yuji</au><au>He, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Environment-stimulated nanocarriers enabling multi-active sites for high drug encapsulation as an "on demand" drug release system</atitle><jtitle>Journal of materials chemistry. B, Materials for biology and medicine</jtitle><addtitle>J Mater Chem B</addtitle><date>2018-04-21</date><risdate>2018</risdate><volume>6</volume><issue>15</issue><spage>2258</spage><epage>2273</epage><pages>2258-2273</pages><issn>2050-750X</issn><eissn>2050-7518</eissn><abstract>Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensitive polyethylene glycol and imidazole to construct bioreducible nanocarriers (PLM-
g
-ss-EGA). The uniform spherical shape and high stability of the PLM-
g
-ss-EGA nanocarriers were demonstrated by dynamic light scattering (DLS) and dissipative particle dynamics (DPD) simulations. Enhanced interaction between the monomers in this novel nanocarrier doubled its drug loading efficiency (15%) as compared to that of traditional polyester nanocarriers (5-7%). Moreover, stimulus-responsive assessment and
in vitro
drug release studies showed that these bioreducible nanocarriers can balance extracellular stability in blood circulation and intracellular "on demand" release.
In vitro
and
in vivo
assays have demonstrated that these bioreducible nanocarriers not only can substantially enhance antitumor efficacy as compared to insensitive micelles and even comparably to free DOX·HCl, but can also greatly reduce unwanted side effects in other organs. The encouraging anticancer efficiency of these poly(malic acid)-based nanocarriers opens a new avenue to design multifunctional biodegradable polyester drug-delivery systems.
Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>32254566</pmid><doi>10.1039/c8tb00132d</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-5591-2299</orcidid><orcidid>https://orcid.org/0000-0003-3041-3933</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2050-750X |
| ispartof | Journal of materials chemistry. B, Materials for biology and medicine, 2018-04, Vol.6 (15), p.2258-2273 |
| issn | 2050-750X 2050-7518 |
| language | eng |
| recordid | cdi_rsc_primary_c8tb00132d |
| source | Royal Society of Chemistry |
| subjects | Anticancer properties Antitumor activity Biodegradability Biodegradation Blood circulation Drug delivery systems Drug development Dynamic stability Fabrication Imidazole Intracellular Light scattering Monomers Organs Photon correlation spectroscopy Polyester resins Polyesters Polyethylene glycol Polymalic acid Side effects Therapeutic applications |
| title | Environment-stimulated nanocarriers enabling multi-active sites for high drug encapsulation as an "on demand" drug release system |
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