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Immunogenic cancer cell death triggered by free and polymer bound doxorubicin
Kabešová, Martina ; Kovář, Lubomír (advisor) ; Anděra, Ladislav (referee)
Immunogenic cancer cell death triggered by free and polymer-bound doxorubicin Water-soluble polymeric drug carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) have been developed to avoid undesirable side-effects of systemically active cytostatic drugs. Conjugates based on HPMA copolymer passively accumulate in tumor tissue of solid tumors due to the effect of enhanced vascular permeability and retention effect (EPR effect). Active accumulation can be achieved by binding of targeting structure recognising tumor-specific receptors to the polymeric carrier. Conjugation of free doxorubicin to HPMA polymeric carrier significantly reduces its nonspecific side effects in vivo by maintaining effective antitumor activity in vitro and in vivo. Besides direct cytotoxic effect on tumor cells, HPMA conjugates with bound doxorubicin possess immunostimulatory properties and induce long-lasting anti-tumor immunity in cured mice. Recent studies have shown that free doxorubicin induce immunogenic apoptosis in tumor cells. Those cells are dying by cell death which possesses characteristic markers of apoptosis but these cells are able to activate the immune system and thus induce effective anti-tumor immune response. This phenomenon has been described as crucial for a development of treatment-induced...
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Immunogenic cancer cell death triggered by free and polymer bound doxorubicin
Kabešová, Martina ; Kovář, Lubomír (advisor) ; Anděra, Ladislav (referee)
Immunogenic cancer cell death triggered by free and polymer-bound doxorubicin Water-soluble polymeric drug carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) have been developed to avoid undesirable side-effects of systemically active cytostatic drugs. Conjugates based on HPMA copolymer passively accumulate in tumor tissue of solid tumors due to the effect of enhanced vascular permeability and retention effect (EPR effect). Active accumulation can be achieved by binding of targeting structure recognising tumor-specific receptors to the polymeric carrier. Conjugation of free doxorubicin to HPMA polymeric carrier significantly reduces its nonspecific side effects in vivo by maintaining effective antitumor activity in vitro and in vivo. Besides direct cytotoxic effect on tumor cells, HPMA conjugates with bound doxorubicin possess immunostimulatory properties and induce long-lasting anti-tumor immunity in cured mice. Recent studies have shown that free doxorubicin induce immunogenic apoptosis in tumor cells. Those cells are dying by cell death which possesses characteristic markers of apoptosis but these cells are able to activate the immune system and thus induce effective anti-tumor immune response. This phenomenon has been described as crucial for a development of treatment-induced...
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Glykosylace povrchové membrány EL-4 buněk: vliv volného nebo N-(2-hydroxypropyl)methacrylamide (HPMA) vázaného doxorubicinu
Kovář, Lubomír ; Etrych, Tomáš ; Šubr, Vladimír ; Strohalm, Jiří ; Sklenář, Jan ; Chytil, Petr ; Ulbrich, Karel ; Říhová, Blanka
In those experimenst we studied the possible impace of CD43 as highly glycosylated molecule in cells exposed to free doxorubicin (Dox) or to conjugates consisting of HPMA copolymer backbone to which the drug is conjugated via enzymatically (PK1 conjugate) or pH sensitive, hydrolytically cleavable bond (hydrazone conjugate, HYD).
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