Intracellular delivery of bioactive molecules using light-addressable nanocapsules

利用光寻址纳米胶囊进行细胞内生物活性分子递送

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作者:Kimberly A D Gregersen, Zachary B Hill, Jennifer C Gadd, Bryant S Fujimoto, Dustin J Maly, Daniel T Chiu

Abstract

This paper describes a method by which molecules that are impermeable to cells are encapsulated in dye-sensitized lipid nanocapsules for delivery into cells via endocytosis. Once inside the cells, the molecules are released from the lipid nanocapsules into the cytoplasm with a single nanosecond pulse from a laser in the far red (645 nm). We demonstrate this method with the intracellular release of the second messenger IP(3) in CHO-M1 cells and report that calcium responses from the cells changed from a sustained increase to a transient spike when the average number of IP(3) released is decreased below 50 molecules per nanocapsule. We also demonstrate the delivery of a 23 kDa O(6)-alkylguanine-DNA alkyltransferase (AGT) fusion protein into Ba/F3 cells to inhibit a key player BCR-ABL in the apoptotic pathway. We show that an average of ∼8 molecules of the inhibitor is sufficient to induce apoptosis in the majority of Ba/F3 cells.

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