Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer-alendronate-taxane conjugate.
A polymer therapeutic designed for combination anticancer and antiangiogenic therapy inhibited the proliferation of prostate carcinoma cells and the proliferation, migration, and tube-formation of endothelial cells. The nanoconjugate was formed from an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, the bisphosphonate alendronate (for bone targeting), and the chemotherapy agent paclitaxel (PTX), which is cleaved by cathepsin B (see scheme).
Miller
Keren
K
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Erez
Rotem
R
Segal
Ehud
E
Shabat
Doron
D
Satchi-Fainaro
Ronit
R
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry*; D019386:Alendronate / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001952:Bridged-Ring Compounds / Q000737:chemistry; D002401:Cathepsin B / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D043823:Taxoids / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000178:Acrylamides; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; C541324:HPMA copolymer-PTX-FK-ALN conjugate; D011108:Polymers; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; C080625:taxane; D002401:Cathepsin B; D017239:Paclitaxel; C032976:N-(2-hydroxypropyl)methacrylamide; D019386:Alendronate