Iron-crosslinked Rososome with robust stability and high drug loading for synergistic cancer therapy

JOURNAL OF CONTROLLED RELEASE

卷:329

Article

Xue, Xiangdong¹  Ricci, Marina^1,2  Qu, Haijing¹  Lindstrom, Aaron¹  Zhang, Dalin¹  Wu, Hao¹  Lin, Tzu-Yin³  Li, Yuanpei¹ 

[1] Univ Calif Davis, UC Davis Comprehens Canc Ctr, Dept Biochem & Mol Med, Sacramento, CA 95817 USA

[2] Univ Torino, Dept Clin & Biol Sci, Corso Raffaello 30, I-10125 Turin, Italy

[3] Univ Calif Davis, Dept Internal Med, Div Hematol Oncol, Sacramento, CA 95817 USA

关键词: Chemotherapy;    Liposome;    Synergistic effect;    Crosslink;    Drug delivery;   

DOI  :  10.1016/j.jconrel.2020.10.013

来源: Elsevier

【 摘 要 】

Development of liposomal nanomedicine with robust stability, high drug loading and synergistic efficacy is a promising strategy for effective cancer therapy. Here, we present an iron-crosslinked rosmarinic liposome (Rososome) which can load high contents of drugs (including 25.8% rosmarinic acid and 9.04% doxorubicin), keep stable in a high concentration of anionic detergent and exhibit synergistic anti-cancer efficacy. The Rososomes were constructed by rosmarinic acid-lipid conjugates which not only work synergistically with doxorubicin by producing reactive oxygen species but also provide catechol moieties for the iron cross-linkages. The cross-linkages can lock the payloads tightly, endowing the crosslinked Rososome with better stability and pharmacokinetics than its non-crosslinked counterpart. On the syngeneic mouse model of breast cancer, the iron-crosslinked Rososomes exhibit better anticancer efficacy than free rosmarinic acid, doxorubicin, non-crosslinked Rososome and commercial liposomal formulation of doxorubicin (DOXIL). This study introduces a novel strategy for the development of liposomes with robust stability, high drug loading and synergistic anti-cancer efficacy.

【 授权许可】

Free