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.
Institut für Medizinische Virologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
M
M
Michaelis
J
J
Matousek
J U
JU
Vogel
T
T
Slavik
K
K
Langer
J
J
Cinatl
J
J
Kreuter
D
D
Schwabe
J
J
Cinatl
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