Publications by authors named "Shoji Tachikawa"

9 Publications

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Effective photodynamic therapy in drug-resistant prostate cancer cells utilizing a non-viral antitumor vector (a secondary publication).

Laser Ther 2016 Mar;25(1):55-62

Graduate School of Engineering, Osaka University; Global Center for Medical Engineering and Informatics, Osaka University; Graduate School of Frontier Biosciences, Osaka University.

Background And Aims: There is an urgent need to develop an efficient strategy for the treatment of drug-resistant prostate cancer. Photodynamic therapy (PDT), in which low incident levels of laser energy are used to activate a photosensitizer taken up by tumor cells, is expected as a novel therapy for the treatment of prostate cancer because of the minimal invasive nature of PDT. The present study was designed to assess the efficacy of a novel vector approach combined with a conventional porphyrin-based photosensitizer.

Materials And Methods: Our group focused on a non-viral vector (hemagglutinating virus of Japan envelope; HVJ-E) combined with protoporphyrin IX (PpIX) lipid, termed the porphyrus envelope (PE). It has been previously confirmed that HVJ-E has drug-delivering properties and can induce cancer-specific cell death. The PE (HVJ-E contained in PpIX lipid) was developed as a novel photosensitizer. In this study, the antitumor and PDT efficacy of the PE against hormone-antagonistic human prostate cancer cells (PC-3) were evaluated.

Results And Conclusions: Our results demonstrated that, under specific circumstances, PDT using the PE was very effective against PC-3 cells. A novel therapy for drug-resistant prostate cancer based on this vector approach is eagerly anticipated.
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http://dx.doi.org/10.5978/islsm.16-OR-05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846841PMC
March 2016

Localization-dependent cell-killing effects of protoporphyrin (PPIX)-lipid micelles and liposomes in photodynamic therapy.

Bioorg Med Chem 2015 Dec 2;23(24):7578-84. Epub 2015 Nov 2.

Chemical Research Laboratory, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan. Electronic address:

The protoporphyron (PPIX)-lipid (PL-C17) liposomes were successfully prepared from the corresponding micelles by post-inserted method. Both the PL-C17 micelles and liposomes were distributed in plasma membrane and cytoplasm after incubation of the cells with PL-C17 liposomes for 1h. They translocated from plasma membrane into a certain organelle in the cells after incubation in the photosensitizer-free medium. Higher photo-cytotoxicity was observed in the PL-C17 micelles and liposomes localized in plasma membrane in comparison with those localized in the cytoplasm under light irradiation. The LDH assay revealed that cytopathic damages of the plasma membrane were observed in the PL-C17 micelles and liposomes highly localized in plasma membrane. The fluorescent intensity of the calcein-encapsulating DOPC liposomes post-inserted with PL-C17 increased after light irradiation, suggesting that the membrane disruption is possibly caused by oxidation of membrane lipids with ROS generated from photosensitizers and affects the photo-cytotoxicity in PDT.
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http://dx.doi.org/10.1016/j.bmc.2015.11.001DOI Listing
December 2015

Spermidinium closo-dodecaborate-encapsulating liposomes as efficient boron delivery vehicles for neutron capture therapy.

Chem Commun (Camb) 2014 Oct;50(82):12325-8

Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.

closo-Dodecaborate-encapsulating liposomes were developed as boron delivery vehicles for neutron capture therapy. The use of spermidinium as a counter cation of closo-dodecaborates was essential not only for the preparation of high boron content liposome solutions but also for efficient boron delivery to tumors.
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http://dx.doi.org/10.1039/c4cc04344hDOI Listing
October 2014

Synthesis of protoporphyrin-lipids and biological evaluation of micelles and liposomes.

Bioorg Med Chem 2014 Sep 9;22(17):4745-51. Epub 2014 Jul 9.

Chemical Research Laboratory, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan. Electronic address:

Protoporphyrin IX (PPIX) lipids were synthesized by introducing a long alkyl chain, such as C13, C15, and C17, at each vinyl group on PPIX via hydrobromination. The PPIX lipids exhibited a water-soluble property by forming their micelles in water and the PPIX-lipid micelles showed relatively low cytotoxicity toward HeLa cells (IC50=151.7-379.9μM) without light irradiation. PL-C17 liposomes (post-inserted liposomes) were readily prepared by adding PL-C17 micelle solution to the liposome solution. The IC50 values of PPIX, PL-C17 micelles, and PL-C17 liposomes toward HeLa cells were 0.53, 5.65, and 12.9μM, respectively, after irradiation with a xenon lamp in the 400-800nm range for 2min. PL-C17 liposomes were selectively accumulated in the Golgi apparatus in cells.
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http://dx.doi.org/10.1016/j.bmc.2014.07.003DOI Listing
September 2014

Amphiphilic COSAN and I2-COSAN crossing synthetic lipid membranes: planar bilayers and liposomes.

Chem Commun (Camb) 2014 Jun;50(51):6700-3

Laboratory of Molecular Biophysics, Dept. of Physics, Universitat Jaume I, 12071 Castelló, Spain.

The boron-rich cobaltabisdicarbollide (COSAN) and its 8,8'-I2 derivative (I2-COSAN), both of purely inorganic nature, are shown to cross through synthetic lipid membranes. These results reveal unexpected properties at the interface of biological and synthetic membranes.
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http://dx.doi.org/10.1039/c4cc01283fDOI Listing
June 2014

A novel photodynamic therapy for drug-resistant prostate cancer cells using porphyrus envelope as a novel photosensitizer.

Photodiagnosis Photodyn Ther 2014 Mar 19;11(1):48-54. Epub 2013 Oct 19.

Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan; The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Background: In the clinic, it is often very difficult to treat drug-resistant advanced prostate cancer by conventional treatments. Photodynamic therapy (PDT) is a minimally invasive treatment that takes advantage of photochemical reactions between a photosensitizer and light. On the basis of several of its key characteristics, PDT is considered to be a promising novel method for treating drug-resistant prostate cancer.

Objectives: For effective treatment of drug-resistant prostate cancer, we developed a novel agent termed porphyrus envelope, which was produced from PpIX lipid and hemagglutinating virus of Japan envelope (HVJ-E).

Materials And Methods: We inserted PpIX lipid into HVJ-E by centrifugation, and used the resultant porphyrus envelope in PDT of two drug-resistant prostate cancer cell lines, PC-3 and PC-3-DR.

Results: Porphyrus envelope enhanced uptake of PpIX, and cytotoxicity of PDT, relative to free PpIX lipid or PpIX induced by 5-ALA.

Conclusion: PDT using porphyrus envelope has potential as a method for treating drug-resistant prostate cancer.
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http://dx.doi.org/10.1016/j.pdpdt.2013.10.001DOI Listing
March 2014

Towards new boron carriers for boron neutron capture therapy: metallacarboranes bearing cobalt, iron and chromium and their cholesterol conjugates.

Bioorg Med Chem 2013 Mar 5;21(5):1136-42. Epub 2013 Jan 5.

Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa Str., Lodz 93-232, Poland.

A method for the synthesis of cholesterol-metallacarborane conjugates bearing cobalt, iron and chromium was developed. Effective incorporation of the cholesterol conjugate bearing cobalt into liposome membrane was revealed. Using the metallacarborane-encrusted liposomes as boron delivery system in vivo biodistribution experiments in tumor-bearing mice, high accumulation and selective delivery of boron into tumor tissues was observed. The results demonstrate that the cholesterol-metallacarborane conjugates can be considered as a potential candidate for boron delivery vehicle in BNCT.
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http://dx.doi.org/10.1016/j.bmc.2012.12.039DOI Listing
March 2013

Development of high boron content liposomes and their promising antitumor effect for neutron capture therapy of cancers.

Bioconjug Chem 2013 Jan 19;24(1):124-32. Epub 2012 Dec 19.

Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Toshima-ku, Tokyo 171-8588, Japan.

Mercaptoundecahydrododecaborate (BSH)-encapsulating 10% distearoyl boron lipid (DSBL) liposomes were developed as a boron delivery vehicle for neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in addition to its encapsulated agents. BSH-encapsulating 10% DSBL liposomes have high boron content (B/P ratio: 2.6) that enables us to prepare liposome solution with 5000 ppm boron concentration. BSH-encapsulating 10% DSBL liposomes displayed excellent boron delivery efficacy to tumor: boron concentrations reached 174, 93, and 32 ppm at doses of 50, 30, and 15 mg B/kg, respectively. Magnescope was also encapsulated in the 10% DSBL liposomes and the real-time biodistribution of the Magnescope-encapsulating DSBL liposomes was measured in a living body using MRI. Significant antitumor effect was observed in mice injected with BSH-encapsulating 10% DSBL liposomes even at the dose of 15 mg B/kg; the tumor completely disappeared three weeks after thermal neutron irradiation ((1.5-1.8) × 10(12) neutrons/cm(2)). The current results enabled us to reduce the total dose of liposomes to less than one-fifth compared with that of the BSH-encapsulating liposomes without reducing the efficacy of boron neutron capture therapy (BNCT).
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http://dx.doi.org/10.1021/bc300527nDOI Listing
January 2013

Design and synthesis of fluorescence-labeled closo-dodecaborate lipid: its liposome formation and in vivo imaging targeting of tumors for boron neutron capture therapy.

Org Biomol Chem 2012 Feb 23;10(7):1374-80. Epub 2011 Dec 23.

Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo, 171-8588, Japan.

The fluorescence-labeled closo-dodecaborane lipid (FL-SBL) was synthesized from (S)-(+)-1,2-isopropylideneglycerol as a chiral starting material. FL-SBL was readily accumulated into the PEGylated DSPC liposomes prepared from DSPC, CH, and DSPE-PEG-OMe by the post insertion protocol. The boron concentrations and the fluorescent intensities of the FL-SBL-labeled DSPC liposomes increased with the increase of the additive FL-SBL, and the maximum emission wavelength of the liposomes appeared at 531 nm. A preliminary in vivo imaging study of tumor-bearing mice revealed that the FL-SBL-labeled DSPC liposomes were delivered to the tumor tissue but not distributed to hypoxic regions.
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http://dx.doi.org/10.1039/c1ob06500aDOI Listing
February 2012