Aptamer-Conjugated Multifunctional Polymeric Nanoparticles as Cancer-Targeted, MRI-Ultrasensitive Drug Delivery Systems for Treatment of Castration-Resistant Prostate Cancer
Nanoscopic therapeutic systems that incorporate therapeutic agents, molecular targeting, and imaging capabilities have gained momentum and exhibited significant therapeutic potential. In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer-targeted capability, an...
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| creator | Lin, Shudong Situ, Jie Yang, Fei Lin, Shaoxiong Fang, Youqiang Luo, Yun |
| description | Nanoscopic therapeutic systems that incorporate therapeutic agents, molecular targeting, and imaging capabilities have gained momentum and exhibited significant therapeutic potential. In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer-targeted capability, and efficient magnetic resonance imaging (MRI) contrast characteristics were formulated and applied in the treatment of castration-resistant prostate cancer (CRPC). The “core-shell” targeted nanoparticles (NPs) were synthesized by the self-assembly of a prefunctionalized amphiphilic triblock copolymer composed of poly(lactic-co-glycolic-acid) (PLGA), polyethylene glycol (PEG), and the Wy5a aptamer (Apt), which have been screened for targeting the CRPC cell line PC-3 by cell-SELEX technique as described in our previous study. Docetaxel (Dtxl) and a cluster of hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles were simultaneously encapsulated into the targeted nanoparticles. The targeted NPs showed a controlled drug release and an increased contrast-enhanced MRI capability. The presence of Wy5a on the nanoparticle surface resulted in the cancer-targeted delivery to PC-3 cells in vitro and in vivo. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI and increased cytotoxicity of these targeted NPs. In vivo studies revealed that the targeted NPs exhibited a more efficacious antitumor capability without significant systemic toxicity. Our data suggested that these targeted NPs may be a promising drug delivery system for the efficacious treatment of CRPC. |
| doi_str_mv | 10.1155/2020/9186583 |
| format | Article |
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In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer-targeted capability, and efficient magnetic resonance imaging (MRI) contrast characteristics were formulated and applied in the treatment of castration-resistant prostate cancer (CRPC). The “core-shell” targeted nanoparticles (NPs) were synthesized by the self-assembly of a prefunctionalized amphiphilic triblock copolymer composed of poly(lactic-co-glycolic-acid) (PLGA), polyethylene glycol (PEG), and the Wy5a aptamer (Apt), which have been screened for targeting the CRPC cell line PC-3 by cell-SELEX technique as described in our previous study. Docetaxel (Dtxl) and a cluster of hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles were simultaneously encapsulated into the targeted nanoparticles. The targeted NPs showed a controlled drug release and an increased contrast-enhanced MRI capability. The presence of Wy5a on the nanoparticle surface resulted in the cancer-targeted delivery to PC-3 cells in vitro and in vivo. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI and increased cytotoxicity of these targeted NPs. In vivo studies revealed that the targeted NPs exhibited a more efficacious antitumor capability without significant systemic toxicity. Our data suggested that these targeted NPs may be a promising drug delivery system for the efficacious treatment of CRPC.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2020/9186583</identifier><identifier>PMID: 32420382</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Aptamers ; Aptamers, Nucleotide - chemistry ; Aptamers, Nucleotide - pharmacokinetics ; Aptamers, Nucleotide - pharmacology ; Biocompatibility ; Block copolymers ; Cancer therapies ; Care and treatment ; Castration ; Chemical compounds ; Contrast agents ; Contrast Media - chemistry ; Contrast Media - pharmacokinetics ; Contrast Media - pharmacology ; Copolymers ; Cytotoxicity ; Delayed-Action Preparations - chemistry ; Delayed-Action Preparations - pharmacokinetics ; Delayed-Action Preparations - pharmacology ; Docetaxel - chemistry ; Docetaxel - pharmacokinetics ; Docetaxel - pharmacology ; Drug Carriers - chemistry ; Drug Carriers - pharmacokinetics ; Drug Carriers - pharmacology ; Drug delivery ; Drug delivery systems ; Drugs ; Health aspects ; Humans ; Hydrophobicity ; In vivo methods and tests ; Iron oxides ; Ligands ; Magnetic fields ; Magnetic Resonance Imaging ; Male ; Medical imaging ; Medical prognosis ; Nanoparticles ; Nanoparticles - chemistry ; Nanoparticles - therapeutic use ; PC-3 Cells ; Pharmacology ; Polyethylene glycol ; Polylactide-co-glycolide ; Polymers ; Polyols ; Prostate cancer ; Prostatic Neoplasms, Castration-Resistant - diagnostic imaging ; Prostatic Neoplasms, Castration-Resistant - drug therapy ; Prostatic Neoplasms, Castration-Resistant - metabolism ; Self-assembly ; Toxicity ; Vehicles</subject><ispartof>BioMed research international, 2020, Vol.2020 (2020), p.1-12</ispartof><rights>Copyright © 2020 Youqiang Fang et al.</rights><rights>COPYRIGHT 2020 John Wiley & Sons, Inc.</rights><rights>Copyright © 2020 Youqiang Fang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Youqiang Fang et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-68a3afdbf29787eb1f246b1ef2aa9c15a0d130ad12daf063dd96c0d519b7baf3</citedby><cites>FETCH-LOGICAL-c499t-68a3afdbf29787eb1f246b1ef2aa9c15a0d130ad12daf063dd96c0d519b7baf3</cites><orcidid>0000-0003-3539-3310 ; 0000-0002-2768-5949 ; 0000-0001-7814-4889 ; 0000-0002-3124-2905</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201588/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201588/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32420382$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhou, Jinyuan</contributor><creatorcontrib>Lin, Shudong</creatorcontrib><creatorcontrib>Situ, Jie</creatorcontrib><creatorcontrib>Yang, Fei</creatorcontrib><creatorcontrib>Lin, Shaoxiong</creatorcontrib><creatorcontrib>Fang, Youqiang</creatorcontrib><creatorcontrib>Luo, Yun</creatorcontrib><title>Aptamer-Conjugated Multifunctional Polymeric Nanoparticles as Cancer-Targeted, MRI-Ultrasensitive Drug Delivery Systems for Treatment of Castration-Resistant Prostate Cancer</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Nanoscopic therapeutic systems that incorporate therapeutic agents, molecular targeting, and imaging capabilities have gained momentum and exhibited significant therapeutic potential. In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer-targeted capability, and efficient magnetic resonance imaging (MRI) contrast characteristics were formulated and applied in the treatment of castration-resistant prostate cancer (CRPC). The “core-shell” targeted nanoparticles (NPs) were synthesized by the self-assembly of a prefunctionalized amphiphilic triblock copolymer composed of poly(lactic-co-glycolic-acid) (PLGA), polyethylene glycol (PEG), and the Wy5a aptamer (Apt), which have been screened for targeting the CRPC cell line PC-3 by cell-SELEX technique as described in our previous study. Docetaxel (Dtxl) and a cluster of hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles were simultaneously encapsulated into the targeted nanoparticles. The targeted NPs showed a controlled drug release and an increased contrast-enhanced MRI capability. The presence of Wy5a on the nanoparticle surface resulted in the cancer-targeted delivery to PC-3 cells in vitro and in vivo. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI and increased cytotoxicity of these targeted NPs. In vivo studies revealed that the targeted NPs exhibited a more efficacious antitumor capability without significant systemic toxicity. Our data suggested that these targeted NPs may be a promising drug delivery system for the efficacious treatment of CRPC.</description><subject>Aptamers</subject><subject>Aptamers, Nucleotide - chemistry</subject><subject>Aptamers, Nucleotide - pharmacokinetics</subject><subject>Aptamers, Nucleotide - pharmacology</subject><subject>Biocompatibility</subject><subject>Block copolymers</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Castration</subject><subject>Chemical compounds</subject><subject>Contrast agents</subject><subject>Contrast Media - chemistry</subject><subject>Contrast Media - pharmacokinetics</subject><subject>Contrast Media - pharmacology</subject><subject>Copolymers</subject><subject>Cytotoxicity</subject><subject>Delayed-Action Preparations - chemistry</subject><subject>Delayed-Action Preparations - pharmacokinetics</subject><subject>Delayed-Action Preparations - pharmacology</subject><subject>Docetaxel - chemistry</subject><subject>Docetaxel - pharmacokinetics</subject><subject>Docetaxel - pharmacology</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Carriers - pharmacokinetics</subject><subject>Drug Carriers - pharmacology</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Drugs</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hydrophobicity</subject><subject>In vivo methods and tests</subject><subject>Iron oxides</subject><subject>Ligands</subject><subject>Magnetic fields</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medical prognosis</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Nanoparticles - therapeutic use</subject><subject>PC-3 Cells</subject><subject>Pharmacology</subject><subject>Polyethylene glycol</subject><subject>Polylactide-co-glycolide</subject><subject>Polymers</subject><subject>Polyols</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms, Castration-Resistant - diagnostic imaging</subject><subject>Prostatic Neoplasms, Castration-Resistant - drug therapy</subject><subject>Prostatic Neoplasms, Castration-Resistant - metabolism</subject><subject>Self-assembly</subject><subject>Toxicity</subject><subject>Vehicles</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkk1v1DAQhiMEolXpjTOyxJGG-iPJJhek1ZZCpRaqspytiT1OvUrire0U7Y_qf8SrXZZywxePxs-882o8WfaW0Y-MleU5p5yeN6yuylq8yI65YEVesYK9PMRCHGWnIaxoOjWraFO9zo4ELzgVNT_OnubrCAP6fOHG1dRBRE1upj5aM40qWjdCT25dv0mIVeQbjG4NPlrVYyAQyAJGlYqX4DtMpWfk5u4q_9lHDwHHYKN9RHLhp45cYJ9ivyE_NiHiEIhxniw9QhxwjMSZJBVS2bZlfofBhggpf-tdCiLuG73JXhnoA57u75Nsefl5ufiaX3__crWYX-eqaJqYVzUIMLo1vJnVM2yZ4UXVMjQcoFGsBKqZoKAZ12BoJbRuKkV1yZp21oIRJ9mnnex6agfUKjn00Mu1twP4jXRg5b8vo72XnXuUM05ZWddJ4P1ewLuHCUOUKzf5NMsgeUEpnxVCPKM66FHa0bgkpgYblJxXvKGlKEuRqLMdpdIsgkdz8MGo3C6B3C6B3C9Bwt89936A_3x5Aj7sgHs7avhl_1MOE4MG_tJM1JRx8Rt_EMff</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Lin, Shudong</creator><creator>Situ, Jie</creator><creator>Yang, Fei</creator><creator>Lin, Shaoxiong</creator><creator>Fang, Youqiang</creator><creator>Luo, Yun</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>3V.</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3539-3310</orcidid><orcidid>https://orcid.org/0000-0002-2768-5949</orcidid><orcidid>https://orcid.org/0000-0001-7814-4889</orcidid><orcidid>https://orcid.org/0000-0002-3124-2905</orcidid></search><sort><creationdate>2020</creationdate><title>Aptamer-Conjugated Multifunctional Polymeric Nanoparticles as Cancer-Targeted, MRI-Ultrasensitive Drug Delivery Systems for Treatment of Castration-Resistant Prostate Cancer</title><author>Lin, Shudong ; Situ, Jie ; Yang, Fei ; Lin, Shaoxiong ; Fang, Youqiang ; Luo, Yun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-68a3afdbf29787eb1f246b1ef2aa9c15a0d130ad12daf063dd96c0d519b7baf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aptamers</topic><topic>Aptamers, Nucleotide - chemistry</topic><topic>Aptamers, Nucleotide - pharmacokinetics</topic><topic>Aptamers, Nucleotide - pharmacology</topic><topic>Biocompatibility</topic><topic>Block copolymers</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Castration</topic><topic>Chemical compounds</topic><topic>Contrast agents</topic><topic>Contrast Media - chemistry</topic><topic>Contrast Media - pharmacokinetics</topic><topic>Contrast Media - pharmacology</topic><topic>Copolymers</topic><topic>Cytotoxicity</topic><topic>Delayed-Action Preparations - chemistry</topic><topic>Delayed-Action Preparations - pharmacokinetics</topic><topic>Delayed-Action Preparations - pharmacology</topic><topic>Docetaxel - chemistry</topic><topic>Docetaxel - pharmacokinetics</topic><topic>Docetaxel - pharmacology</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Carriers - pharmacokinetics</topic><topic>Drug Carriers - pharmacology</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Drugs</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hydrophobicity</topic><topic>In vivo methods and tests</topic><topic>Iron oxides</topic><topic>Ligands</topic><topic>Magnetic fields</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medical prognosis</topic><topic>Nanoparticles</topic><topic>Nanoparticles - 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In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer-targeted capability, and efficient magnetic resonance imaging (MRI) contrast characteristics were formulated and applied in the treatment of castration-resistant prostate cancer (CRPC). The “core-shell” targeted nanoparticles (NPs) were synthesized by the self-assembly of a prefunctionalized amphiphilic triblock copolymer composed of poly(lactic-co-glycolic-acid) (PLGA), polyethylene glycol (PEG), and the Wy5a aptamer (Apt), which have been screened for targeting the CRPC cell line PC-3 by cell-SELEX technique as described in our previous study. Docetaxel (Dtxl) and a cluster of hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles were simultaneously encapsulated into the targeted nanoparticles. The targeted NPs showed a controlled drug release and an increased contrast-enhanced MRI capability. The presence of Wy5a on the nanoparticle surface resulted in the cancer-targeted delivery to PC-3 cells in vitro and in vivo. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI and increased cytotoxicity of these targeted NPs. In vivo studies revealed that the targeted NPs exhibited a more efficacious antitumor capability without significant systemic toxicity. Our data suggested that these targeted NPs may be a promising drug delivery system for the efficacious treatment of CRPC.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>32420382</pmid><doi>10.1155/2020/9186583</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-3539-3310</orcidid><orcidid>https://orcid.org/0000-0002-2768-5949</orcidid><orcidid>https://orcid.org/0000-0001-7814-4889</orcidid><orcidid>https://orcid.org/0000-0002-3124-2905</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | BioMed research international, 2020, Vol.2020 (2020), p.1-12 |
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| language | eng |
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| subjects | Aptamers Aptamers, Nucleotide - chemistry Aptamers, Nucleotide - pharmacokinetics Aptamers, Nucleotide - pharmacology Biocompatibility Block copolymers Cancer therapies Care and treatment Castration Chemical compounds Contrast agents Contrast Media - chemistry Contrast Media - pharmacokinetics Contrast Media - pharmacology Copolymers Cytotoxicity Delayed-Action Preparations - chemistry Delayed-Action Preparations - pharmacokinetics Delayed-Action Preparations - pharmacology Docetaxel - chemistry Docetaxel - pharmacokinetics Docetaxel - pharmacology Drug Carriers - chemistry Drug Carriers - pharmacokinetics Drug Carriers - pharmacology Drug delivery Drug delivery systems Drugs Health aspects Humans Hydrophobicity In vivo methods and tests Iron oxides Ligands Magnetic fields Magnetic Resonance Imaging Male Medical imaging Medical prognosis Nanoparticles Nanoparticles - chemistry Nanoparticles - therapeutic use PC-3 Cells Pharmacology Polyethylene glycol Polylactide-co-glycolide Polymers Polyols Prostate cancer Prostatic Neoplasms, Castration-Resistant - diagnostic imaging Prostatic Neoplasms, Castration-Resistant - drug therapy Prostatic Neoplasms, Castration-Resistant - metabolism Self-assembly Toxicity Vehicles |
| title | Aptamer-Conjugated Multifunctional Polymeric Nanoparticles as Cancer-Targeted, MRI-Ultrasensitive Drug Delivery Systems for Treatment of Castration-Resistant Prostate Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T12%3A29%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Aptamer-Conjugated%20Multifunctional%20Polymeric%20Nanoparticles%20as%20Cancer-Targeted,%20MRI-Ultrasensitive%20Drug%20Delivery%20Systems%20for%20Treatment%20of%20Castration-Resistant%20Prostate%20Cancer&rft.jtitle=BioMed%20research%20international&rft.au=Lin,%20Shudong&rft.date=2020&rft.volume=2020&rft.issue=2020&rft.spage=1&rft.epage=12&rft.pages=1-12&rft.issn=2314-6133&rft.eissn=2314-6141&rft_id=info:doi/10.1155/2020/9186583&rft_dat=%3Cgale_pubme%3EA629053553%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2400274338&rft_id=info:pmid/32420382&rft_galeid=A629053553&rfr_iscdi=true |