Conjugation of chlorins with spermine enhances phototoxicity to cancer cells in vitro

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F17%3A43913328" target="_blank" >RIV/60461373:22330/17:43913328 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/ijphotobiol.2017.02.012" target="_blank" >http://dx.doi.org/10.1016/ijphotobiol.2017.02.012</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/ijphotobiol.2017.02.012" target="_blank" >10.1016/ijphotobiol.2017.02.012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Conjugation of chlorins with spermine enhances phototoxicity to cancer cells in vitro

Popis výsledku v původním jazyce

Photodynamic therapy (PDT) is one of the most promising methods of specific cancer treatment. However, commercially available photosensitizers (PSs) show significant drawbacks, such as side toxicity, low penetration ability, low blood solubility, low tumor selectivity etc. In addition, as was shown previously, a conjugation of polyamines with several toxic agents led to an increased toxicity to cancer cells. Here, we synthesized conjugates of two chlorine photosensitizers, purpurin 18 and pheophorbide a, with spermine in natural and Boc-protected form. Using specialized software, we calculated octanol-water partition coefficients for single protonation state (logP) of single PSs and PS/spermine conjugates. We found that the addition of spermine to chlorine PSs shifted the logP towards higher hydrophilicity in comparison to logP of single chlorines. In vitro studies on several cancer cells indicated that conjugation of purpurin 18 with spermine increased its retention in cancer cells. Using various concentrations of this conjugate, we found that lower concentrations (under 02 mu M) of purpurin 18/spermine conjugate launched apoptosis in HeLa cells. This combined with its high phototoxicity makes the purpurin 18/spermine conjugate a promising photosensitizer for PDT. Obtained results might serve as a basis for further studies of this potential third-generation PS on mammalian models in vivo.

Název v anglickém jazyce

Conjugation of chlorins with spermine enhances phototoxicity to cancer cells in vitro

Popis výsledku anglicky

Photodynamic therapy (PDT) is one of the most promising methods of specific cancer treatment. However, commercially available photosensitizers (PSs) show significant drawbacks, such as side toxicity, low penetration ability, low blood solubility, low tumor selectivity etc. In addition, as was shown previously, a conjugation of polyamines with several toxic agents led to an increased toxicity to cancer cells. Here, we synthesized conjugates of two chlorine photosensitizers, purpurin 18 and pheophorbide a, with spermine in natural and Boc-protected form. Using specialized software, we calculated octanol-water partition coefficients for single protonation state (logP) of single PSs and PS/spermine conjugates. We found that the addition of spermine to chlorine PSs shifted the logP towards higher hydrophilicity in comparison to logP of single chlorines. In vitro studies on several cancer cells indicated that conjugation of purpurin 18 with spermine increased its retention in cancer cells. Using various concentrations of this conjugate, we found that lower concentrations (under 02 mu M) of purpurin 18/spermine conjugate launched apoptosis in HeLa cells. This combined with its high phototoxicity makes the purpurin 18/spermine conjugate a promising photosensitizer for PDT. Obtained results might serve as a basis for further studies of this potential third-generation PS on mammalian models in vivo.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10400 - Chemical sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Photochemistry and Photobiology B: Biology

ISSN

1011-1344

e-ISSN

—

Svazek periodika

168

Číslo periodika v rámci svazku

březen 2017

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

175-184

Kód UT WoS článku

000397689500022

EID výsledku v databázi Scopus

2-s2.0-85013393674