第６回 iCONM 学術セミナーのご案内
平素から大変お世話になっております。
ナノ医療イノベーションセンター（iCONM）では、プロジェクト COINS の終了に伴い、これまで開催してきました「COINS セミナー」を「iCONM 学術セミナー」と改称し、引き続き開催させて頂くこととなりました。弊センターの公開イベントとして、他に「市民公開講座」を開催しておりますが、「iCONM 学術セミナー」は、より専門的で学術的な内容のものと位置付けております。
第６回目は、アイスランド大学より Már Másson 教授をお迎えし、以下に記す要領で 11/30 午前１０時より開催致します。Másson 教授の専門は医薬品化学で、特に甲殻類の殻から取れるキトサンを中心とした創薬研究を行っています。今回の講演では、Photochemical Internalization(PCI) 技術を用いたがん治療がテーマとなります。PCI は、両親媒性の光増感剤を用いて細胞内へ薬剤を送達する技術で、光をトリガーとして部位特異的に治療が行えるという点で注目されています。
オンラインでの開催となりますので、事前登録によりアクセスに必要な URL を入手頂けますようお願い致します。今後ともホットな内容にフォーカスを充てた企画を立てていく所存ですので、引き続きよろしくお願い致します。
2022 年 11 月 18 日ナノ医療イノベーションセンターイノベーション推進チーム
記
日時︓2022 年 11 月 30 日 9 時 45 分開場 10 時 00 分開演
場所︓ZOOM によるオンライン開催
演題︓Selective synthesis of chitosan nano-conjugates for photochemicalinternalization cancer therapy
講師︓Dr. Már Másson
Professor Medicinal Chemistry, Faculty of Pharmaceutical Sciences,
School of Health Sciences, University of Iceland
言語︓英語
事前申込み︓
https://iconm.kawasaki-net.ne.jp/form/academic-seminar6/
講師略歴︓Már Másson, completed BS in chemistry from theUniversity of Iceland in 1987,Cand. Scient (MS)organic chemistry, Copenhagen University, Denmarkin 1990 andDoctor of Engineering – Biotechnology

from Tokyo Institute of Technology, Japan, in 1995.
He became Post-Doc at the University of Iceland Department of Pharmacy in 1995,
Assoc. Prof. in medicinal chemistry in 1998 and since 2005 he has been a Professor
in Medicinal Chemistry at the University of Iceland, Faculty of PharmaceuticalSciences.
The research group headed by Már Másson is mainly focused on the synthesis andinvestigation of chitosan derivatives. The group developed TBDMS protection
strategy for chitosan that can be utilized for chemoselective and highly controlled
synthesis of chitosan derivatives. The applications that have been investigated are:chitosan derivatives as antimicrobial agents, chitosan derivatives as permeation
enhancers affecting tight junctions in the pulmonary epithelium, chitosan
nanocarriers for photochemical internalization, and chitosan derivatives as coatings
for application in regenerative medicine. Már Másson also collaborates withengineers and mathematicians in Iceland focusing on developing a numericalframework for modeling drug delivery systems including transdermal andophthalmic drug delivery systems and and bioelectronics based on chitosan.
講演要旨︓
Photochemical internalization (PCI) is a novel technology, which utilizes selected
photosensitizers (PS) in combination with light excitation, to induce the release of
endocytosed hydrophilic drugs so they can reach their target before being degradedin lysosomes. This therapy has been shown to be effective in the clinic but theefficiency could potentially be further improved with polymeric nanocarriers. Thesewould allow for tumor-selective accumulation due to the enhanced permeation andretention (EPR) effect. The aim of the current study was to develop the synthesis
and investigate nanoconjugates, that were composed of cationic chitosan
derivatives with covalently linked highly lipophilic photosensitizers. TBDMSprotected chitosan was utilized for the efficient synthesis of highly substituted
nanoconjugates. The proof-of-concept study was done with tetraphenylporphyrin(TPP) as the photosensitizer [1]. The nanoconjugate structure and degree ofsubstitution was determined by 1-H and solid-state NMR. Physiochemical
characteristics were also investigated by fluorescence, dynamic light scattering, andsize exclusion chromatography. The nano-conjugates formed nanoparticle-likestructures with an average size of nanoparticles in the range of 100-300 nm. TheTPP nanoconjugates were effective for PCI-mediated gene delivery in a human colon
carcinoma cell line.
The more challenging tetraphenylchlorin (TPC) conjugates were also synthesized[2]. These offer the advantage of possible activation and longer wavelengths (650nm) and are therefore suitable for in vivo use. A dynamic light scattering (DLS)
study confirmed the formation of nanoparticles with a 140–200 nm diameter. These
nanoconjugates were taken up and localized in the endocytic vesicles ofHCT116/LUC human colon carcinoma cells, and upon illumination, they substantiallyenhanced plasmid DNA transfection. The nanoconjugates were also evaluated inpreliminary in vivo experiments in tumor-bearing mice, showing that thenanoconjugates could induce strong photodynamic therapy (PDT) and also PCI
effects in treatment with bleomycin.
The TPC conjugates were also used to develop biodegradable polymericnanoparticles (NPs) containing the cytostatic drugs mertansine (MRT) or cabazitaxel(CBZ) [3]. The TPC–CS NPs had high loading capacity and strong drug retentiondueto π–πstacking interactions between thedrugsand

thearomatic

photosensitizer groups of the polymers. The TPC–CS NPs loaded with MRT or CBZ
displayed higher cytotoxicity than the free form of these drugs in the breast cancer
cell lines MDA-MB-231 and MDA-MB-468. Biodistribution studies in mice showedthat most of the TPC–CS NPs accumulated in the liver and lungs, but they were also
found to be localized in tumors derived from HCT-116 cells. These data suggest thatthe drug-loaded TPC–CS NPs have potential in combinatory anticancer therapy andas contrast agents.
[1] Vivek S. Gaware, Monika Håkerud , Kristján Leósson, Sigríður Jónsdóttir, Anders Høgset, Kristian Berg,Már Másson (2013). Tetraphenylporphyrin Tethered Chitosan Based Carriers for Photochemical Transfection.
Journal of Medicinal Chemistry56, 807−819 (dx.doi.org/10.1021/jm301270r)[2] Vivek S. Gaware, Monika Håkerud, Asta Juzeniene, Anders Høgset, Kristian Berg, Már Másson. (2017)
Endosome Targeting meso-Tetraphenylchlorin-Chitosan Nano-Conjugates for Photochemical Internalization
Biomacromolecules 18 (4), 1108-1126 ( https://doi.org/10.1021/acs.biomac.6b01670 )[3]Abhilash D. Pandya, Anders Øverbye, Priyanka Sahariah, Vivek S. Gaware, Håkon Høgset, Màr Masson,

Anders Høgset, Gunhild M. Mælandsmo, Tore Skotland, Kirsten Sandvig, and Tore-Geir Iversen*. (2020)
Drug-loaded Photosensitizer-Chitosan Conjugate Nanoparticles for Combinatorial chemo- and photodynamic
therapy in Breast Cancer Cells. – Biomacromolecules(https://doi.org/10.1021/acs.biomac.0c00061)

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