Bovine seminal ribonuclease attached to nanoparticles made of polylactic acid kills leukemia and lymphoma cell lines in vitro.
Bovine seminal ribonuclease (BS-RNase) is a protein with a number of biological effects. It shows antitumoral, aspermatogenic, antiembryonic, immunosuppressive and antiviral properties. The cytotoxic effects appear to be specific for tumor cells as non-malignant cells seem to be unaffected in vitro. Unfortunately, the in vivo application of BS-RNase so far was successful only when it was administered intratumorally. Therefore, the objective of the present investigation was to improve the properties of BS-RNase by attachment to nanoparticles made of polylactic acid (PLA-NP) using an adsorption method. This preparation was tested in vitro against leukemia (MOLT-4) and lymphoma (H9) cell lines sensitive and resistant to cytarabine. No difference between the nanoparticle preparation and pure BS-RNase was found in these tests. To examine the in vivo effects, the preparations were tested for their aspermatogenic and antiembryonal efficacy compared to the pure BS-RNase as a rapid test for antitumoral activity. The aspermatogenic and antiembryonal effects were enhanced by the nanoparticle preparation. Consequently, BS-RNase loaded adsorptively to PLA-NP holds promise for the in vivo use as an antitumoral agent. Further research will investigate the efficacy of this preparations in an in vivo tumor model.
Michaelis
M
M
Institut für Medizinische Virologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
Matousek
J
J
Vogel
J U
JU
Slavik
T
T
Langer
K
K
Cinatl
J
J
Kreuter
J
J
Schwabe
D
D
Cinatl
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004722:Endoribonucleases / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid; D007938:Leukemia / Q000188:drug therapy*; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D011091:Polyesters; D011108:Polymers; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D013778:Tetrazolium Salts; D013844:Thiazoles; D019344:Lactic Acid; C033616:poly(lactide); D004722:Endoribonucleases; C032523:ribonuclease SPL; C022616:thiazolyl blue