Examples of Tumor Growth Inhibition Properties of Liposomal Formulations of pH-Sensitive Histidinylated Cationic Amphiphiles

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• 作者：Arup Garu ; Gopikrishna Moku ; Suresh Kumar Gulla ; Dipankar Pramanik ; Bharat K. Majeti ; Priya P. Karmali ; Haseena Shaik ; Bojja Sreedhar ; Arabinda Chaudhuri
• 刊名：ACS Biomaterials Science & Engineering
• 出版年：2015
• 出版时间：August 10, 2015
• 年：2015
• 卷：1
• 期：8
• 页码：646-655
• 全文大小：627K
• ISSN：2373-9878

文摘

Herein we report on the unexpected cancer cell selective cytotoxicities of the liposomal formulations of aspartic and glutamic acid backbone-based four novel lipids with endosomal pH-sensitive head-groups and aliphatic n-hexadecyl & n-octadecyl hydrophobic tails. Surprisingly, although the formulations killed cancer cells efficiently, they were significantly less cytotoxic in non-cancerous healthy cells. Importantly, intratumoral administration of the liposomal formulations efficiently inhibited growth of melanoma in a syngeneic C57BL/6J mouse tumor model. Western Blotting experiments with the lysates of liposomes treated cancer cells revealed that liposomes of lipids 1–4 induce apoptosis selectively in cancer cells presumably by releasing cytochrome c from depolarized mitochondria and subsequent activation of caspases 3 & 9, upregulation of Bax and down regulation of Bcl-2. In summary, the present report describes for the first time tumor growth inhibition properties of the liposomal formulations of endosomal pH-sensitive histidinylated cationic lipids under both in vitro and systemic settings.