The effects of novel polymeric therapeutics based on water-soluble N-(2-hydroxypropyl)methacrylamide copolymers (P(HPMA)) bearing the anticancer drug doxorubicin (Dox), an inhibitor of ABC transporters, or both, on the viability and the proliferation of the murine monocytic leukemia cell line P388 (parental cell line) and its doxorubicin-resistant subline P388/MDR were studied in vitro. The inhibitor derivatives 5-methyl-4-oxohexanoyl reversin 121 (MeOHe-R121) and 5-methyl-4-oxohexanoyl ritonavir ester (MeOHe-RIT), showing the highest inhibitory activities, were conjugated to the P(HPMA) via the biodegradable pH-sensitive hydrazone bond, and the ability of these conjugates to block the ATP driven P-glycoprotein (P-gp) efflux pump was tested. The P(HPMA) conjugate P-Ahx-NH-N═MeOHe-R121 showed a dose-dependent increase in the ability to sensitize the P388/MDR cells to Dox from 1.5 to 24 μM, and achieved an approximately 50-fold increase in sensitization at 24 μM. The P(HPMA) conjugate P-Ahx-NH-N═MeOHe-RIT showed moderate activity at 6 μM (∼10 times higher sensitization) and increased sensitization by 50-fold at 12 μM. The cytostatic activity of the P(HPMA) conjugate P-Ahx-NH-N═MeOHe-R121(Dox) containing Dox and the P-gp inhibitor MeOHe-R121, both bound via hydrazone bonds to the P(HPMA) carrier, was almost 30 times higher than that of the conjugate P-Ahx-NH-N═Dox toward the P388/MDR cells in vitro. A similar result was observed for P-Ahx-NH-N═MeOHe-RIT(Dox), which exhibited almost 10 times higher cytostatic activity than P-Ahx-NH-N═Dox.
- MeSH
- ABC transportéry antagonisté a inhibitory MeSH
- akrylamidy chemická syntéza MeSH
- antibiotika antitumorózní farmakologie MeSH
- chemorezistence * MeSH
- doxorubicin farmakologie MeSH
- hydrazony chemie MeSH
- koncentrace vodíkových iontů MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- P-glykoprotein metabolismus MeSH
- systémy cílené aplikace léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportéry MeSH
- akrylamidy MeSH
- antibiotika antitumorózní MeSH
- doxorubicin MeSH
- hydrazony MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- P-glykoprotein MeSH
Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent longlasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms.
- MeSH
- antigeny CD80 metabolismus MeSH
- antigeny CD86 metabolismus MeSH
- antitumorózní látky aplikace a dávkování chemie toxicita MeSH
- apoptóza účinky léků MeSH
- chemorezistence účinky léků MeSH
- dendritické buňky cytologie imunologie MeSH
- doxorubicin aplikace a dávkování analogy a deriváty chemie toxicita MeSH
- fagocytóza MeSH
- kalretikulin metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kyseliny polymethakrylové aplikace a dávkování chemie toxicita MeSH
- lymfom T-buněčný farmakoterapie imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemie MeSH
- protein HMGB1 metabolismus MeSH
- proteiny tepelného šoku metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD80 MeSH
- antigeny CD86 MeSH
- antitumorózní látky MeSH
- doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
- doxorubicin MeSH
- kalretikulin MeSH
- kyseliny polymethakrylové MeSH
- nosiče léků MeSH
- protein HMGB1 MeSH
- proteiny tepelného šoku MeSH
Novel star polymer-doxorubicin conjugates designed for passive tumor targeting have been developed and their potential for treatment of cancer has been investigated. In the present study the synthesis, physico-chemical characterization, drug release, bio-distribution and preliminary data of in vivo efficacy of the conjugates are described. In the water-soluble conjugates the core of a molecule formed by poly(amido amine) (PAMAM) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing doxorubicin (Dox) attached by hydrazone bonds enabling intracellular pH-controlled hydrolytic drug release, or by GFLG sequence susceptible to enzymatic degradation. The controlled synthesis utilizing semitelechelic copolymer precursors facilitated preparation of polymer conjugates in a broad range of molecular weights (1.1-3.0·10(5) g/mol). In contrast to free drug or linear conjugates the star polymer-Dox conjugates exhibited prolonged blood circulation and enhanced tumor accumulation in tumor-bearing mice indicating important role of the EPR effect. The star polymer-Dox conjugates showed significantly higher anti-tumor activity in vivo than Dox?HCl or its linear or graft polymer conjugates, if treated with a single dose 15 or 5 mg Dox eq./kg. Method of tumor initialization (acute or chronic experimental tumor models) significantly influenced effectiveness of the treatment with much lower success in treatment of mice bearing chronic tumors.
- MeSH
- akrylamidy chemie MeSH
- antibiotika antitumorózní aplikace a dávkování chemie farmakokinetika MeSH
- dendrimery chemie MeSH
- doxorubicin aplikace a dávkování chemie farmakokinetika MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem MeSH
- lymfom T-buněčný farmakoterapie patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nosiče léků chemie MeSH
- rozpustnost MeSH
- systémy cílené aplikace léků * MeSH
- tkáňová distribuce MeSH
- voda chemie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- akrylamidy MeSH
- antibiotika antitumorózní MeSH
- dendrimery MeSH
- doxorubicin MeSH
- léky s prodlouženým účinkem MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- nosiče léků MeSH
- PAMAM Starburst MeSH Prohlížeč
- voda MeSH
A systematic study was designed to elucidate differences in cytostatic activity in vitro between HPMA-based doxorubicin conjugates synthesized using different polymerization techniques and differing in peptidyl side chain. A polymer-drug conjugate containing doxorubicin (DOX) bound to HPMA copolymer backbone through the enzymaticaly non-cleavable sequence GlyGly shows low but significant cytotoxicity in vitro in seven cancer cell lines of mouse (EL4, 38C13, 3T3, BCL1) and human (SW620, Raji, Jurkat) origin. The low cytotoxicity can be considerably increased by the presence of additional drug-free GlyPheLeuGly side chains. P1 conjugate, i.e. non-targeted HPMA copolymer bearing doxorubicin bound via a biodegradable GlyPheLeuGly sequence, synthesized by direct copolymerization of HPMA with monomeric doxorubicin and thus without additional drug-free GlyPheLeuGly sequences is less effective compared to PK1 synthesized by polymer analogous reaction and thus containing extra drug-free GlyPheLeuGly sequences. Significant activity-enhancing effect was not seen with other amino acid/oligopeptide sequences (e.g., Gly or GlyGly). The activity-enhancing effect of GlyPheLeuGly sequences is more obvious in the conjugate containing doxorubicin bound to HPMA through GlyGly sequence. Derivatization of the terminal carboxyl group of the extra GlyPheLeuGly side chains (amide, N-substituted amide, free carboxyl) does not significantly influence the cytotoxicity of the conjugates. The presence of the GlyPheLeuGly sequence in the conjugate structure increases its rate of intracellular accumulation. Normal cells (Balb/c splenocytes) accumulate less polymer-doxorubicin conjugate compared to cancer cells (T cell lymphoma EL4, B cell lymphoma Raji and T cell leukemia JURKAT).
- MeSH
- antibiotika antitumorózní farmakologie MeSH
- apoptóza MeSH
- doxorubicin analogy a deriváty farmakologie MeSH
- kultivované buňky MeSH
- kyseliny polymethakrylové farmakologie MeSH
- lidé MeSH
- methakryláty chemie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nekróza MeSH
- oligopeptidy chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- slezina cytologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibiotika antitumorózní MeSH
- doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
- doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Prohlížeč
- kyseliny polymethakrylové MeSH
- methakryláty MeSH
- oligopeptidy MeSH
Conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) represent a new generation of antibody-targeted polymeric anticancer drugs with both cytotoxic and immunoprotecting/immunomobilizing activity. 20-90% of mice that are cured of EL4 mouse T-cell lymphoma, BCL1 mouse B-cell leukaemia and 38C13 mouse B-cell lymphoma by injection of doxorubicin-HPMA conjugate develop a long-lasting memory and systemic antitumour resistance. It is suggested that the main activity of the polymeric drug, directly after application is - due to the high level of the drug - of cytotoxic and cytostatic nature. Thereafter, long-term conjugates persist at low concentration in the circulation, which are capable of mobilizing the defence mechanisms of the host. Until now, seven patients with generalized carcinoma were treated with doxorubicin-HPMA-human-Ig conjugate. Disease stabilization, lasting from 6 to more than 18 months, was recorded.
- MeSH
- antibiotika antitumorózní farmakokinetika farmakologie MeSH
- doxorubicin farmakokinetika farmakologie MeSH
- lidé MeSH
- methakryláty farmakokinetika farmakologie MeSH
- nádory farmakoterapie imunologie MeSH
- přirozená imunita * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antibiotika antitumorózní MeSH
- doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Prohlížeč
- methakryláty MeSH
The hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for RNase A or BS-RNase modification to prevent their degradation in bloodstream or fast elimination. Two PHPMA chains (classic and star-like) were synthesized and their conjugates with both enzymes were tested on the CD-1 nude mice bearing various human tumors. These RNase conjugates injected intravenously or intraperitoneally into the mice bearing melanoma, neuroblastoma or ovarian tumor caused significant reduction of transplanted tumors following ten daily doses of 2.5 and/or 1 mg/kg, respectively, while free RNase A or BS-RNase injected in doses of 10 mg/kg exerted only negligible antitumor activity. Histological examination confirmed potent cytotoxic effect of RNase A conjugates in ovarian tumor. Despite the antitumor activity observed in vivo, the in vitro cytotoxic activity of RNase A conjugates was not pronounced and did not differ from that caused by the free RNase A. The in vitro experiments with 125I-labeled preparations demonstrated that polymer conjugates were internalized by tumor cells very poorly in contrast to the dose-dependent internalization of the wild enzyme preparation. Surprisingly, mice injected with EL-4 leukemic cells, which were preincubated for 4 h with BS-RNase conjugates, exerted significantly prolonged survival compared with the control non-treated mice. It may be supposed that both BS-RNase and RNase A conjugates with PHPMA act after administration in vivo by a mechanism different from that or those occurring under in vitro conditions because in vivo they exert an antitumor action, whereas in vitro, they are ineffective. The experiments proved that RNase A, when conjugated to PHPMA, produced identical aspermatogenic and antitumor effects as BS-RNase conjugated to this polymer and that this preparation may be regarded as a potential anticancer drug.
- MeSH
- antitumorózní látky * aplikace a dávkování imunologie MeSH
- buněčné dělení účinky léků MeSH
- ELISA MeSH
- injekce intraperitoneální MeSH
- injekce intravenózní MeSH
- lidé MeSH
- methakryláty MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádory vaječníků farmakoterapie MeSH
- neuroblastom farmakoterapie MeSH
- pankreas enzymologie MeSH
- pankreatická ribonukleasa aplikace a dávkování imunologie farmakologie MeSH
- polymery MeSH
- ribonukleasy aplikace a dávkování imunologie farmakologie MeSH
- skot MeSH
- sperma enzymologie MeSH
- spermatogeneze účinky léků MeSH
- těhotenství MeSH
- teratogeny farmakologie MeSH
- transplantace nádorů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- skot MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky * MeSH
- hydroxypropyl methacrylate MeSH Prohlížeč
- methakryláty MeSH
- pankreatická ribonukleasa MeSH
- polymery MeSH
- ribonukleasy MeSH
- teratogeny MeSH
N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing the anticancer drug doxorubicin and targeted with B1 monoclonal antibody (mAb) to BCL1 leukemia cells was synthesised and tested in vitro and in vivo. BCL1 leukemia growing in syngenic Balb/c mice was selected as a tumor model system. B1 mAb recognising the idiotype of surface IgM on BCL1 cells was used as a targeting moiety. Both B1 mAb and doxorubicin were conjugated to HPMA copolymer carrier by aminolysis through a tetrapeptidic Gly-Phe(D,L)-Leu-Gly spacer to ensure the intracellular delivery and controlled release of the drug. B1 mAb-targeted conjugate was shown to possess strictly tumor-specific binding capacity to target BCL1 cells in vitro. A similar conjugate, but containing human nonspecific Ig (HuIg) instead of B1 mAb, failed to bind to BCL1 cells. In vitro, B1 mAb-targeted conjugate demonstrated 40-fold higher cytotoxic effect than nontargeted or human nonspecific Ig-containing HPMA copolymer-bound doxorubicin. Conjugate targeted with B1 mAb was also shown to bind to target BCL1 cells in vivo. B1 mAb-targeted conjugate was shown to be more efficient in the treatment of established BCL1 leukemia than free doxorubicin, nontargeted and human nonspecific Ig-containing conjugate. Antibody-targeted polymeric drugs are thus promising conjugates for cancer treatment.
- MeSH
- akrylamidy chemie terapeutické užití MeSH
- antigeny nádorové imunologie MeSH
- buněčné dělení účinky léků MeSH
- doxorubicin chemie terapeutické užití MeSH
- hydrogely chemie MeSH
- imunokonjugáty krev farmakologie terapeutické užití MeSH
- inhibiční koncentrace 50 MeSH
- injekce intraperitoneální MeSH
- injekce intravenózní MeSH
- leukemie B-buněčná farmakoterapie imunologie mortalita MeSH
- leukocyty mononukleární chemie MeSH
- míra přežití MeSH
- monoklonální protilátky analýza chemie farmakologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- počet retikulocytů MeSH
- protilátky anti-idiotypické analýza chemie farmakologie MeSH
- průtoková cytometrie MeSH
- slezina chemie MeSH
- systémy cílené aplikace léků metody MeSH
- tělesná hmotnost účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylamidy MeSH
- antigeny nádorové MeSH
- doxorubicin MeSH
- hydrogely MeSH
- imunokonjugáty MeSH
- monoklonální protilátky MeSH
- N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate MeSH Prohlížeč
- protilátky anti-idiotypické MeSH
Recently hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for BS-RNase modification to prevent its degradation in bloodstream or fast elimination. Polymer-conjugated BS-RNase preparations proved to be cytotoxic after intravenous or intraperitoneal application, whereas native BS-RNase was ineffective. Here RNase A unimer was conjugated with two HPMA polymers (classic and star) and their antitumor effects both in vitro and in vivo were compared with those of BS-RNase polymers. Surprisingly, the antitumor effect of RNase A conjugates was also pronounced. The RNase A conjugates (classic and star) injected intravenously to mice bearing melanoma tumor caused a significant reduction in tumor volume following ten doses of 5 and 1 mg/kg, respectively. Despite the antitumor activity observed in vivo, the in vitro tested cytotoxic activity of RNase A did not differ from that caused by native RNase A while native BS-RNase (50 microg/ml) totally inhibited DNA synthesis in treated cells. The experiments with 125I-labeled preparations demonstrated concentration-dependent internalization of native BS-RNase by tumor cells within an hour, whereas the polymer conjugate (S-BS) was not internalized. On the contrary, the in vivo experiments showed that whereas 40% of S-BS conjugate persisted in bloodstream for 24h after administration, 98% of the native BS-RNase was already eliminated. Improved antitumor activities of PHPMA-modified RNases in vivo might be ascribed to their prolonged retention in bloodstream, better proteolytic stability and resistance to the action of the ribonuclease inhibitor.
- MeSH
- antitumorózní látky aplikace a dávkování chemie terapeutické užití MeSH
- endoribonukleasy aplikace a dávkování chemie terapeutické užití MeSH
- injekce intraperitoneální MeSH
- injekce intravenózní MeSH
- konformace proteinů MeSH
- kyseliny polymethakrylové aplikace a dávkování chemie MeSH
- lidé MeSH
- lymfocyty metabolismus MeSH
- melanom experimentální farmakoterapie patologie MeSH
- molekulární struktura MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované metabolismus MeSH
- nosiče léků MeSH
- pankreatická ribonukleasa aplikace a dávkování chemie terapeutické užití MeSH
- radioizotopy jodu MeSH
- skot MeSH
- vazebná místa fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- způsoby aplikace léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- skot MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky MeSH
- Duxon MeSH Prohlížeč
- endoribonukleasy MeSH
- kyseliny polymethakrylové MeSH
- nosiče léků MeSH
- pankreatická ribonukleasa MeSH
- radioizotopy jodu MeSH
- ribonuclease SPL MeSH Prohlížeč
Internalization and subcellular fate of free doxorubicin or its polymeric conjugates based on poly N-(2-hydroxypropyl)methacrylamide (pHPMA), either non-targeted or targeted with anti-Thy1.2 or anti-CD71 monoclonal antibody was tested on EL-4 mouse T-cell lymphoma, SW620 human colorectal carcinoma and OVCAR-3 human ovarian adenocarcinoma. Doxorubicin fluorescence allowed us to follow the internalization and intracellular distribution of tested conjugates by laser scanning confocal microscopy and/or by fluorescent microscopy. Whereas free doxorubicin was always detectable only in the nuclei of treated cells, detectable fluorescence of doxorubicin bound to a polymeric carrier, targeted or non-targeted, was detectable up to 3 days of incubation only in the cytoplasmatic structures. While free doxorubicin causes apoptosis in the populations of tested cancer cell lines, significant number of apoptotic cells was never found in cell cultures exposed to targeted or non-targeted polymeric conjugates. In contrast to free doxorubicin, which is a strong inducer of p53 expression, increased p53 expression was never observed after the treatment with the polymeric drug. High-performance liquid chromatographic analysis shows that the percentage of cleaved doxorubicin is very low even after 48 h of incubation of tested cells with the polymeric conjugate, and cannot be the only reason for the toxicity of the conjugate. We suggest that: (a) after the treatment with pHPMA-bound drug, the cells die by necrosis and (b) the toxicity of pHPMA-based conjugates is a combination of the toxic effect of released doxorubicin and the toxic effect of doxorubicin in polymer-bound form directed against cell membranes.
- MeSH
- antitumorózní látky farmakokinetika MeSH
- buněčné jádro metabolismus MeSH
- doxorubicin farmakokinetika MeSH
- geny p53 fyziologie MeSH
- intracelulární membrány metabolismus MeSH
- lidé MeSH
- myši MeSH
- nádorové buňky kultivované metabolismus MeSH
- polymery chemie farmakokinetika MeSH
- viabilita buněk účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antitumorózní látky MeSH
- doxorubicin MeSH
- polymery MeSH
N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing the anticancer agent doxorubicin and targeted to the transferrin receptor either with anti-mouse CD71 monoclonal antibody (mAb) or with transferrin were synthesized to evaluate their binding and anti-proliferative activity in vitro and anti-tumor potential against 38C13 B-cell lymphoma in vivo. Both the doxorubicin and the targeting moieties were bound to HPMA copolymer chain by aminolysis via a Gly-Phe(D,L)-Leu-Gly spacer to ensure controlled intracellular release of the conjugated drug. We demonstrated that HPMA copolymer-bound doxorubicin targeted to the transferrin receptor with anti-mouse CD71 mAb strongly retards tumor growth, prolongs the survival and completely cures three out of nine experimental mice with established 38C13 tumors. The conjugate targeted with transferrin was less effective in vitro as well as in vivo. It completely cured only one out of seven experimental mice. Free or non-targeted HPMA copolymer-bound doxorubicin showed only a mild anti-tumor effect within the therapeutic schedule used. In vitro, HPMA copolymer-bound doxorubicin targeted with anti-mouse CD71 mAb shows approximately 4-fold higher cytotoxic effect than HPMA copolymer-bound doxorubicin targeted with transferin and 9-fold higher cytotoxic effect than non-targeted HPMA copolymer-bound doxorubicin.
- MeSH
- antibiotika antitumorózní aplikace a dávkování chemie farmakologie MeSH
- B-buněčný lymfom metabolismus MeSH
- biotin chemie MeSH
- buněčné dělení MeSH
- doxorubicin aplikace a dávkování chemie farmakologie MeSH
- indikátory a reagencie MeSH
- ligandy MeSH
- methakryláty chemie MeSH
- monoklonální protilátky aplikace a dávkování chemie MeSH
- myši inbrední C3H MeSH
- myši MeSH
- průtoková cytometrie MeSH
- receptory transferinu účinky léků metabolismus MeSH
- transferin aplikace a dávkování chemie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibiotika antitumorózní MeSH
- biotin MeSH
- doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Prohlížeč
- indikátory a reagencie MeSH
- ligandy MeSH
- methakryláty MeSH
- monoklonální protilátky MeSH
- receptory transferinu MeSH
- transferin MeSH