2018年
Macrophage-mediated delivery of light activated nitric oxide prodrugs with spatial, temporal and concentration control
Chemical Science
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- 巻
- 9
- 号
- 15
- 開始ページ
- 3729
- 終了ページ
- 3741
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1039/c8sc00015h
- 出版者・発行元
- Royal Society of Chemistry
© The Royal Society of Chemistry 2018. Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+-doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages. Both the photoNORM [Mn(NO)dpaqNO2]BPh4(dpaqNO2 = 2-[N,N-bis(pyridin-2-yl-methyl)]-amino-N′-5-nitro-quinolin-8-yl-acetamido) and the Nd-UCNPs are activated by tissue-penetrating near-infrared (NIR) light at ∼800 nm. Thus, simultaneous therapeutic NO delivery and photoluminescence (PL) imaging can be achieved with a NIR diode laser source. The loaded microparticles are non-toxic to their macrophage hosts in the absence of light. The microparticle-carrying macrophages deeply penetrate into NIH-3T3/4T1 tumor spheroid models, and when the infiltrated spheroids are irradiated with NIR light, NO is released in quantifiable amounts while emission from the Nd-UCNPs provides images of microparticle location. Furthermore, varying the intensity of the NIR excitation allows photochemical control over NO release. Low doses reduce levels of hypoxia inducible factor 1 alpha (HIF-1α) in the tumor cells, while high doses are cytotoxic. The use of macrophages to carry microparticles with a NIR photo-activated theranostic payload into a tumor overcomes challenges often faced with therapeutic administration of NO and offers the potential of multiple treatment strategies with a single system.
- リンク情報
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- DOI
- https://doi.org/10.1039/c8sc00015h
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/29780505
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939611
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000431389300014&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85045769453&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85045769453&origin=inward
- ID情報
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- DOI : 10.1039/c8sc00015h
- ISSN : 2041-6520
- eISSN : 2041-6539
- ORCIDのPut Code : 48329111
- PubMed ID : 29780505
- PubMed Central 記事ID : PMC5939611
- SCOPUS ID : 85045769453
- Web of Science ID : WOS:000431389300014