Drug delivery mitigates toxic side effects and poor pharmacokinetics of life-saving therapeutics and enhances treatment efficacy. However, direct cytoplasmic delivery of drugs and vaccines into cells has remained out of reach. We find that liposomes studded with 0.8-nm-wide carbon nanotube porins (CNTPs) function as efficient vehicles for direct cytoplasmic drug delivery by facilitating fusion of lipid membranes and complete mixing of the membrane material and vesicle interior content. Fusion kinetics data and coarse-grained molecular dynamics simulations reveal an unusual mechanism where CNTP dimers tether the vesicles, pull the membranes into proximity, and then fuse their outer and inner leaflets. Liposomes containing CNTPs in their membranes and loaded with an anticancer drug, doxorubicin, were effective in delivering the drug to cancer cells, killing up to 90% of them. Our results open an avenue for designing efficient drug delivery carriers compatible with a wide range of therapeutics.

药物输送可减轻救生疗法的毒副作用和不良药代动力学，并提高治疗效果。然而，将药物和疫苗直接通过细胞质输送到细胞中仍然遥不可及。我们发现，布满 0.8 nm 宽碳纳米管孔蛋白 (CNTP) 的脂质体通过促进脂质膜的融合以及膜材料和囊泡内部内容物的完全混合，可作为直接细胞质药物递送的有效载体。融合动力学数据和粗粒度分子动力学模拟揭示了一种不寻常的机制，其中 CNTP 二聚体束缚囊泡，将膜拉近，然后融合其外部和内部小叶。膜中含有 CNTP 并装载有抗癌药物阿霉素的脂质体能够有效地将药物递送至癌细胞，杀死高达 90% 的癌细胞。我们的研究结果为设计与多种治疗方法兼容的高效药物输送载体开辟了一条途径。