Iron-crosslinked Rososome with robust stability and high drug loading for synergistic cancer therapy
Journal of Controlled Release(2021)
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.
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关键词
Chemotherapy,Liposome,Synergistic effect,Crosslink,Drug delivery
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