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      The mitochondria-targeted and IR780-regulated theranosomes for imaging and enhanced photodynamic/photothermal therapy

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          Abstract

          (a) A schematic of the system TPP-IR780/Ce6-TNS. (b) Illustration of the system TPP-IR780/Ce6-TNS to the tumor microenvironment.

          Abstract

          The applications of photodynamic therapy (PDT) are usually limited by the low tumor selectivity of photosensitizers. Herein, we report a near infrared (NIR) imaging multifunctional nanocarrier, so called “theranosome (TNS)”, which encapsulated both chlorin e6 (Ce6, photosensitizer) and IR780 iodide (IR780, photothermal and NIR imaging agent) to realize enhanced PDT efficacy. The phototoxicity of Ce6 was effectively restrained by IR780. Upon NIR laser irradiation at 808 nm, IR780 in the TNS could be degraded, while the phototoxicity of Ce6 could be recovered. In addition, we proved that attaching a triphenylphosphonium (TPP) group to the TNS (TPP-IR780/Ce6-TNS) could greatly facilitate its mitochondrial targeting ability so as to offer a remarkably improved PDT efficacy. This newly constructed TNS exhibited high toxicity to the tumor cells in vitro, indicating TNS was a promising nanocarrier used as a PTT combined activatable PDT.

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          Most cited references16

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          BODIPY dyes in photodynamic therapy.

          BODIPY dyes tend to be highly fluorescent, but their emissions can be attenuated by adding substituents with appropriate oxidation potentials. Substituents like these have electrons to feed into photoexcited BODIPYs, quenching their fluorescence, thereby generating relatively long-lived triplet states. Singlet oxygen is formed when these triplet states interact with (3)O(2). In tissues, this causes cell damage in regions that are illuminated, and this is the basis of photodynamic therapy (PDT). The PDT agents that are currently approved for clinical use do not feature BODIPYs, but there are many reasons to believe that this situation will change. This review summarizes the attributes of BODIPY dyes for PDT, and in some related areas.
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            Targeting antioxidants to mitochondria by conjugation to lipophilic cations.

            Mitochondrial oxidative damage contributes to a range of degenerative diseases. Consequently, the selective inhibition of mitochondrial oxidative damage is a promising therapeutic strategy. One way to do this is to invent antioxidants that are selectively accumulated into mitochondria within patients. Such mitochondria-targeted antioxidants have been developed by conjugating the lipophilic triphenylphosphonium cation to an antioxidant moiety, such as ubiquinol or alpha-tocopherol. These compounds pass easily through all biological membranes, including the blood-brain barrier, and into muscle cells and thus reach those tissues most affected by mitochondrial oxidative damage. Furthermore, because of their positive charge they are accumulated several-hundredfold within mitochondria driven by the membrane potential, enhancing the protection of mitochondria from oxidative damage. These compounds protect mitochondria from damage following oral delivery and may therefore form the basis for mitochondria-protective therapies. Here we review the background and work to date on this class of mitochondria-targeted antioxidants.
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              Gold nanorod-photosensitizer complex for near-infrared fluorescence imaging and photodynamic/photothermal therapy in vivo.

              A gold nanorod (GNR)-photosensitizer complex was developed for noninvasive near-infrared fluorescence imaging and cancer therapy. We showed that (a) fluorescence emission and singlet oxygen generation by AlPcS(4) were quenched after complex formation with GNRs; (b) 4-fold greater intracellular uptake and better in vitro phototoxicity were observed in GNR-AlPcS(4)-treated cells than in free AlPcS(4)-treated cells; and (c) after intravenous injection of the GNR-AlPcS(4) complex, tumor sites were clearly identified on near-infrared fluorescence images as early as 1 h after injection. The tumor-to-background ratio increased over time and was 3.7 at 24 h; tumor growth reduced by 79% with photodynamic therapy (PDT) alone and by 95% with dual photothermal therapy (PTT) and PDT. This novel multifunctional nanomedicine may be useful for near-infrared fluorescence imaging and PTT/PDT in various cancers.
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                Author and article information

                Journal
                RSCACL
                RSC Advances
                RSC Adv.
                Royal Society of Chemistry (RSC)
                2046-2069
                2016
                2016
                : 6
                : 14
                : 11070-11076
                Affiliations
                [1 ]Tianjin Key Laboratory of Drug Delivery & High-Efficiency
                [2 ]School of Pharmaceutical Science and Technology
                [3 ]Tianjin University
                [4 ]Tianjin
                [5 ]PR China
                Article
                10.1039/C5RA19521G
                7decb1f0-f6e1-4cdb-b5e8-44713ebb1dff
                © 2016
                History

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