Алексей Феофанов - Academia.edu (original) (raw)

Uploads

Papers by Алексей Феофанов

Research paper thumbnail of Исследование свойств нового фотосенсибилизатора β,β,β',β'-тетраметилтрибензотетраазахлорина

Химико Фармацевтический Журнал, Feb 28, 2014

1 Ôåäåðàëüíîå ãîñóäàðñòâåííîå óíèòàðíîå ïðåäïðèÿòèå «Ãîñóäàðñòâåííûé íàó÷íûé öåíòð «ÍÈÎÏÈÊ», Ìîñê... more 1 Ôåäåðàëüíîå ãîñóäàðñòâåííîå óíèòàðíîå ïðåäïðèÿòèå «Ãîñóäàðñòâåííûé íàó÷íûé öåíòð «ÍÈÎÏÈÊ», Ìîñêâà, Ðîññèÿ; 2 Ðîññèéñêèé õèìèêî-òåõíîëîãè÷åñêèé óíèâåðñèòåò èì. Ä. È. Ìåíäåëååâà, Ìîñêâà, Ðîññèÿ; 3 Èíñòèòóò áèîîðãàíè÷åñêîé õèìèè èì. àêàä. Ì. Ì. Øåìÿêèíà è Þ. À. Îâ÷èííèêîâà ÐÀÍ, Ìîñêâà, Ðîññèÿ Ïðîâåäåí ñðàâíèòåëüíûé àíàëèç ñîëþáèëèçàòîðîâ Cremophor EL, Tween 80, Ýìóêñîë 3 è Pluronic F-68 ïî ñïîñîáíîñòè îáåñïå÷èâàòü äîñòàâêó ïåðñïåêòèâíîãî ôîòîñåíñèáèëèçàòîðà b,b,b¢,b¢-òåòðàìåòèëòðèáåíçîòåòðààçàõëîðèíà (H 2 TBTAC) â êëåòêè àäåíîêàðöèíîìû ëåãêîãî ÷åëîâåêà À549 in vitro. Îáíàðóaeåíî, ÷òî ñòåïåíü ìîíîìåðíîñòè H 2 TBTAC â ðàñòâîðàõ ðàññìàòðèâàåìûõ ñîëþáèëèçàòîðîâ êîððåëèðóåò ñ êîëè÷åñòâîì ôëóîðåñöèðóþùåãî ìîíîìåðà, íàêàïëèâàþùåãîñÿ â êëåòêàõ. Äîêàçàíà ñóùåñòâåííî áîëåå âûñîêàÿ ñïîñîáíîñòü ìîíîìåðà H 2 TBTAC ê ôîòîèíäóöèðóåìîé ãåíåðàöèè ñèíãëåòíîãî êèñëîðîäà ïî ñðàâíåíèþ ñ àãðåãàòàìè. Óñòàíîâëåíî, ÷òî Cremophor EL îáåñïå÷èâàåò íàèáîëüøóþ ìîíîìåðíîñòü H 2 TBTAC â ðàñòâîðå è íàèëó÷øóþ ñòàáèëüíîñòü êîìïîçèöèè ïðè õðàíåíèè. Cremophor EL ñïîñîáñòâóåò óëó÷øåííîìó íàêîïëåíèþ ìîíîìåðíîãî H 2 TBTAC â öèòîïëàçìå êëåòîê À549 ñ âûõîäîì íà íàñûùåíèå ÷åðåç 2 ÷ èíêóáàöèè è ìàêñèìàëüíûì êîýôôèöèåíòîì íàêîïëåíèÿ H 2 TBTAC ðàâíûì 0,7 ± 0,1.  îïûòàõ in vivo ïîêàçàíî íàëè÷èå òåðàïåâòè÷åñêè çíà÷èìîãî ïðîòèâîîïóõîëåâîãî ýôôåêòà ôîòîäèíàìè÷åñêîé òåðàïèè ñ èñïîëüçîâàíèåì H 2 TBTAC, ñîëþáèëèçèðîâàííîãî â 10 % Cremophor EL. Êëþ÷åâûå ñëîâà: òåòðàìåòèëòðèáåíçîòåòðààçàõëîðèí; âíóòðèêëåòî÷íîå ðàñïðåäåëåíèå; ôîòîñåíñèáèëèçàòîð; ñîëþáèëèçàòîð; ñèíãëåòíûé êèñëîðîä; ôîòîäèíàìè÷åñêàÿ òåðàïèÿ (ÔÄÒ).

Research paper thumbnail of Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage

Biochemical Journal, 2005

Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell types. It is widel... more Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell types. It is widely accepted that the plasma membrane is a target of cytotoxins, but the mechanism of their action remains obscure. Using the confocal spectral imaging technique, we show for the first time that cytotoxins from cobra venom penetrate readily into living cancer cells and accumulate markedly in lysosomes. Cytotoxins CT1 and CT2 from Naja oxiana, CT3 from Naja kaouthia and CT1 from Naja haje are demonstrated to possess this property with respect to human lung adenocarcinoma A549 and promyelocytic leukaemia HL60 cells. Immobilized plasma membrane binding accompanies the internalization of CT3 from Naja kaouthia in the HL60 cells, but it is very weak for other cytotoxins. Detectable membrane binding is not a prop-erty of any of the cytotoxins tested in A549 cells. The kinetics and concentration-dependence of cytotoxin accumulation in lysosomes correlate well with their cytotoxic effects. On the basis of the results obtained, we propose that lysosomes are a primary target of the lytic action of cytotoxins. Plasma membrane permeabilization seems to be a downstream event relative to lysosome rupture. Direct damage to the plasma membrane may be a complementary mechanism, but its relative contribution to the cytotoxic action depends on the cytotoxin structure and cell type.

Research paper thumbnail of Исследование свойств нового фотосенсибилизатора β,β,β',β'-тетраметилтрибензотетраазахлорина

Химико Фармацевтический Журнал, Feb 28, 2014

1 Ôåäåðàëüíîå ãîñóäàðñòâåííîå óíèòàðíîå ïðåäïðèÿòèå «Ãîñóäàðñòâåííûé íàó÷íûé öåíòð «ÍÈÎÏÈÊ», Ìîñê... more 1 Ôåäåðàëüíîå ãîñóäàðñòâåííîå óíèòàðíîå ïðåäïðèÿòèå «Ãîñóäàðñòâåííûé íàó÷íûé öåíòð «ÍÈÎÏÈÊ», Ìîñêâà, Ðîññèÿ; 2 Ðîññèéñêèé õèìèêî-òåõíîëîãè÷åñêèé óíèâåðñèòåò èì. Ä. È. Ìåíäåëååâà, Ìîñêâà, Ðîññèÿ; 3 Èíñòèòóò áèîîðãàíè÷åñêîé õèìèè èì. àêàä. Ì. Ì. Øåìÿêèíà è Þ. À. Îâ÷èííèêîâà ÐÀÍ, Ìîñêâà, Ðîññèÿ Ïðîâåäåí ñðàâíèòåëüíûé àíàëèç ñîëþáèëèçàòîðîâ Cremophor EL, Tween 80, Ýìóêñîë 3 è Pluronic F-68 ïî ñïîñîáíîñòè îáåñïå÷èâàòü äîñòàâêó ïåðñïåêòèâíîãî ôîòîñåíñèáèëèçàòîðà b,b,b¢,b¢-òåòðàìåòèëòðèáåíçîòåòðààçàõëîðèíà (H 2 TBTAC) â êëåòêè àäåíîêàðöèíîìû ëåãêîãî ÷åëîâåêà À549 in vitro. Îáíàðóaeåíî, ÷òî ñòåïåíü ìîíîìåðíîñòè H 2 TBTAC â ðàñòâîðàõ ðàññìàòðèâàåìûõ ñîëþáèëèçàòîðîâ êîððåëèðóåò ñ êîëè÷åñòâîì ôëóîðåñöèðóþùåãî ìîíîìåðà, íàêàïëèâàþùåãîñÿ â êëåòêàõ. Äîêàçàíà ñóùåñòâåííî áîëåå âûñîêàÿ ñïîñîáíîñòü ìîíîìåðà H 2 TBTAC ê ôîòîèíäóöèðóåìîé ãåíåðàöèè ñèíãëåòíîãî êèñëîðîäà ïî ñðàâíåíèþ ñ àãðåãàòàìè. Óñòàíîâëåíî, ÷òî Cremophor EL îáåñïå÷èâàåò íàèáîëüøóþ ìîíîìåðíîñòü H 2 TBTAC â ðàñòâîðå è íàèëó÷øóþ ñòàáèëüíîñòü êîìïîçèöèè ïðè õðàíåíèè. Cremophor EL ñïîñîáñòâóåò óëó÷øåííîìó íàêîïëåíèþ ìîíîìåðíîãî H 2 TBTAC â öèòîïëàçìå êëåòîê À549 ñ âûõîäîì íà íàñûùåíèå ÷åðåç 2 ÷ èíêóáàöèè è ìàêñèìàëüíûì êîýôôèöèåíòîì íàêîïëåíèÿ H 2 TBTAC ðàâíûì 0,7 ± 0,1.  îïûòàõ in vivo ïîêàçàíî íàëè÷èå òåðàïåâòè÷åñêè çíà÷èìîãî ïðîòèâîîïóõîëåâîãî ýôôåêòà ôîòîäèíàìè÷åñêîé òåðàïèè ñ èñïîëüçîâàíèåì H 2 TBTAC, ñîëþáèëèçèðîâàííîãî â 10 % Cremophor EL. Êëþ÷åâûå ñëîâà: òåòðàìåòèëòðèáåíçîòåòðààçàõëîðèí; âíóòðèêëåòî÷íîå ðàñïðåäåëåíèå; ôîòîñåíñèáèëèçàòîð; ñîëþáèëèçàòîð; ñèíãëåòíûé êèñëîðîä; ôîòîäèíàìè÷åñêàÿ òåðàïèÿ (ÔÄÒ).

Research paper thumbnail of Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage

Biochemical Journal, 2005

Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell types. It is widel... more Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell types. It is widely accepted that the plasma membrane is a target of cytotoxins, but the mechanism of their action remains obscure. Using the confocal spectral imaging technique, we show for the first time that cytotoxins from cobra venom penetrate readily into living cancer cells and accumulate markedly in lysosomes. Cytotoxins CT1 and CT2 from Naja oxiana, CT3 from Naja kaouthia and CT1 from Naja haje are demonstrated to possess this property with respect to human lung adenocarcinoma A549 and promyelocytic leukaemia HL60 cells. Immobilized plasma membrane binding accompanies the internalization of CT3 from Naja kaouthia in the HL60 cells, but it is very weak for other cytotoxins. Detectable membrane binding is not a prop-erty of any of the cytotoxins tested in A549 cells. The kinetics and concentration-dependence of cytotoxin accumulation in lysosomes correlate well with their cytotoxic effects. On the basis of the results obtained, we propose that lysosomes are a primary target of the lytic action of cytotoxins. Plasma membrane permeabilization seems to be a downstream event relative to lysosome rupture. Direct damage to the plasma membrane may be a complementary mechanism, but its relative contribution to the cytotoxic action depends on the cytotoxin structure and cell type.