The majority of currently used anticancer drugs belong to the low molecular weight compounds. These medications demonstrate a range of disadvantages, such as fast metabolism and excretion from an organism, as well as adverse biodistribution and a low selectivity of therapeutic use. Solving these problems involves the binding process of drugs with macromolecular carriers. Such structures were designed with the aim to enhance delivery and to improve the selectivity and pharmacological properties of both conventional  and innovative drugs.

In our laboratory antifoliates conjugated with carriers such as dextrans, albumin, fibrinogen and glycated proteins, were examined. Particularly promising investigations pertained  the use of fibrinogen as a  carrier of methotrexate (MTX). Many  prerequisites such as accumulation in tumors  determined  this type of protein to be selected. Fibrinogen-MTX conjugates were characterized by considerably higher anticancer efficacy in comparison to free drug. One of the proposed mechanisms regarding this phenomenon assumes retention of fibrinogen/fibrin and its conjugates in peritoneum of animals with ascites tumors. It also shows a gradual enzymatic  degradation connected to the drug release.  

In this paper we show examination of anticancer properties of the MTX-fibrinogen subjected to limited hydrolysis conjugates in vivo and previously described generation of these conjugates with native fibrinogen. Leukemia mouse model P388  was used in this study, the cancer cells were engrafed intraperitoneally.  High anticancer efficacy of the examined conjugate was observed by prolonging  mice lifespan  at 145% in comparison to lifespan of the control  mice. Accordingly free methotrexate prolonged the lifespan of mice at 36% in comparison to the control mice.  Toxicity  in the dosage pattern of the preparation used was not observed. Data described above emerges a therapeutic potential in drug binding with macromolecular carriers, as well as the potential use of the derived fibrinogen in this system.

This project was supported by National Science Centre, Poland (N N302 098434)

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/28030 must be provided.

1. Synthesis of new 5H-indolo[2,3-b]quinoline derivatives with a high selective cytotoxic activity
2. Administration of isothiocyanate-derived mercapturic acids inhibits solid tumor growth of 4T1 murine mammary carcinoma cells in BALB/c mice
3. Preliminary studies on application of library of artificial receptors for differentiation of metabolites in urine of healthy and cancer mice
4. The effect of ionic strength on the aggregation of bacteriophage T4
5. Starch derivatives as vehicles for drug delivery in anticancer therapy
6. Method for determination of methotrexate (MTX) release from the macromolecular drug-carrier systems in plasma
7. Methods for determination of pemetrexed in macromolecular drug-carrier systems
8. Mercapturic acids as a naturally occurring isothiocyanates prodrug form with site-directed delivery system built-in based on an oxidative environment of the tumor
9. Synthesis and biological activity of novel N,N-cyclic-2,4-dihydroxythiobenzamide derivatives
10. Anticancer activity of vitamin D, genistein and indoloquinoline analogs
11. Synthesis and anticancer activity of acetylenic derivatives of betulin
12. Interaction of endotoxin and polymyxin B in B16 mouse melanoma model of metatstasis
13. ESI-MS/MS techniques for structural analysis of boron clusters
14. Methods for methotrexate determination in macromolecular conjugates drug-carrier
15. Preparation of endotoxin-free bacteriophages from bacterial lysate
16. Synthesis and cytotoxic activity of new Pt (II) complexes with nitropyrazoles in aerobic and hypoxic conditions
17. Vitamin D analogs enhance the activity of imatinib mesylate in human non-small cell lung cancer model
18. Colon cancer treatment with the use of vitamin D analogs and irinotecan 
19. Novel bifunctional synthetic isothiocyanates with high antiproliferative activity
20. Naturally occurring hydroxyalkyl isothiocyanates and isothiocyanatoalkyl benzoates - structure-activity and structure-mechanism of action relationship studies.
21. Synthesis and biological evaluation of new amino acid and dipeptide derivatives of neocryptolepine as anticancer agents. 
22. Antitumor activity of carrier-methotrexate conjugates.
23. CLA derivatives as functional food compounds
24. New acetylenic derivatives of betulin with anticancer activity
25. Catalytic synthesis and antiproliferative activity in vitro of polisubstituted isoxazolopyridine derivatives.
26. Steroid profile of Asplenium cuneifolium
27. The influence of (24R)-1,24- dihydroxyvitamin D₃ on the anticancer activity of 5-fluorouracil in human colon cancer model
28. Comparison of antiproliferative activity of the natural isothiocyanates and their mercapturic derivatives.
29. Could the calorically restricted ketogenic diet be an     effective alternative or supportive therapy for breast cancer?
30. Analogs of genistein and its possible anti-metastatic properties
31. The influence of novel analogs of vitamin D₃ on the antiproliferative activity of cisplatin or doxorubicin on human promyelocytic leukaemia cell line HL-60 
32. New amino acid and peptide derivatives of 5H-indolo[2,3-b]quinoline and their biological activity.
33. The cytotoxic activity of glycosides of indolo[2,3-b]quinoline derivatives.
34. Disubstituted indolo[2,3-b]quinoline derivatives - the cytotoxic activity in vitro against various human tumor cell lines.
35. Mono substituted 5H- and 6H-indolo[2,3-b]quinoline derivatives and their ability to overcome the barrier of drug resistance.
36. Synthesis and antiproliferative activity in vitro of (4-substituted-2-butynylthio)quinolines
37. New calcipotriol analogs, their toxicity and antitumor activity in vivo in comparison to the affinity with VDR and DBP
38. Synthesis and cytostatic activity of new 1-substituted 6H-pyrido[4,3-b]carbazole derivatives
39. The new analogs of genistein decrease mitochondrial membrane potential and activate caspase-3
40. New amino acid derivatives of 6H-indolo[2,3-b]quinolines
41. Influence of Transformation of the Amino Group in Anthracyclines into -N=CH-N< or -N=CH-O- Group on Their Biological Properties
42. PRIMARY CYTOTOXICITY EVALUATION OF NEW HETEROCYCLIC SYSTEMS WITH PYRIDODIAZEPINE.
43. SYNTHESIS AND ANTIPROLIFERATIVE ACTIVITY IN VITRO OF NEW 2-AMINOBENZIMIDAZOLE DERIVATIVES. PART 3. REACTIONS OF 2-ARYLIDENE- AMINOBENZIMIDAZOLE WITH SELECTED 1,3-DIKETONES.
44. ENHANCED STABILITY OF HIGHLY PURE PHAGES WITH BLOCK COPOLYMER OF ETHYLENE OXIDE AND PROPYLENE OXIDE
45. CONJUGATED LINOLEIC ACIDS PREPARATIONS AS EFFECTIVE NUTRACEUTICS
46. THE ANTIMETASTATIC EFFECT OF BACTERIOPHAGE T4* ADMINISTRATED IN COMBINED TREATMENT WITH SELECTED CYTOSTATICS IN MICE WITH B16 MELANOMA
47. SYNTHESIS AND ANTIPROLIFERATIVE ACTIVITY OF DIACETYLENIC THIOQUINOLINES
48. SYNTHESIS AND CYTOTOXIC ACTIVITY OF 10-DEACETYL-10-PROPARGILPACLITAXEL
49. THE CYTOTOXIC GLYCOSIDES OF INDOLO[2,3-B]QUINOLINE DERIVATIVES. IN VITRO AND IN VIVO STUDIES
50. MONO SUBSTITUTED 5H-INDOLO[2,3-B]- QUINOLINE DERIVATIVES AND THEIR ABILITY TO OVERCOME THE BARRIER OF DRUG RESISTANCE.
51. DISUBSTITUTED INDOLO[2,3-b]QUINOLINE DERIVATIVES. THE CYTOTOXIC ACTIVITY IN VITRO AGAINST VARIOUS HUMAN TUMOR CELL LINE.
52. ANTITUMOR EFFECT OF CISPLATIN OR FLUOROURACIL IN COMBINED TREATMENT WITH (24R)-1,24-DIHYDROXYVITA- MIN D₃
53. FIRST ROUND STUDIES ON LEWIS LUNG CARCINOMA ACTIVITY OF THE NEW LEAD STRUCTURES IN THE ISOXAZOLE HETEROCYCLIC SYSTEM
54. CONJUGATES OF METHOTREXATE AND DEXTRANS IN MOUSE LEUKEMIA MODEL WITH MULTIPLE DOSE SCHEDULE
55. GENISTEIN, ITS NEW ANALOGS AND COMPLEXES - THE ANTIPROLIFERATIVE EFFECTS ON HL-60 LEUKEMIA CELL LINE
56. COMBINATION OF: IMATINIB, PRI-2191 AND CYTOSTATICS - THE ANTIPROLIFERATIVE EFFECTS ON HL-60 LEUKEMIA CELL LINE
57. ANTIPROLIFERATIVE ACTIVITY IN VITRO OF DIASTEREOMERIC ANALOGUES OF VITAMIN D3 AGAINST NORMAL AND CANCER CELL LINES