Targeted hydroxyethyl starch prodrug for inhibiting the growth and metastasis of prostate cancer

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• 作者：Kaidong Zhao^a ; ^b ; ^c ; Di Li^b ; Weiguo Xu^b ; Jianxun Ding^b ; ^{jxding@ciac.ac.cn} ; Weiqian Jiang^d ; Mingqiang Li^b ; ^{ml3777@columbia.edu} ; Chunxi Wang^a ; ^{chunxi_wang@126.com} ; Xuesi Chen^b
• 关键词：Hydroxyethyl starch prodrug ; Schiff base bond ; Targeted drug delivery ; Chemotherapy ; Prostate cancer therapy
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：116
• 期：Complete
• 页码：82-94
• 全文大小：4379 K
• 卷排序：116

文摘

Prostate cancer is one of the most prevalent malignancies among men. Although chemotherapy has been an effective therapeutic approach for treating metastatic prostate cancer, serious undesired side effects have hampered its wide application clinically. In this work, a pH-responsive LHRH-conjugated hydroxyethyl starch-doxorubicin (HES-DOX/LHRH) prodrug was facilely synthesized by conjugating oxidized HES (HES-CHO) with DOX and LHRH through an acid-sensitive Schiff base bond. The resulting prodrug spontaneously self-assembled into nanoscopic micelle with a radius of about 55 nm in an aqueous environment. HES-DOX/LHRH significantly improved the in vivo tissue distribution of the drug. Compared to its non-targeted counterpart, targeted HES-DOX/LHRH demonstrated a greater in vitro anti-proliferative capability toward mouse RM-1 prostate cells. More importantly, targeted HES-DOX/LHRH exhibited higher levels of anti-tumor and anti-metastasis activities against an RM-1-xenografted mouse model, with lower systemic toxicity compared to free DOX·HCl and non-targeted HES-DOX. Hence, these results revealed that targeted HES-DOX/LHRH possesses great potential application in clinical chemotherapy of metastatic prostate cancer.