Although several studies have demonstrated repetitive drug release using light-activatable liposomes, inconsistent drug release at each activation limits widespread usage. Here, we report reversible plasmonic material-coated encapsulated liposomes for proportional controlled delivery of methotrexate (MTX), which is a common drug for cancer and autoimmune diseases, using repetitive laser irradiation. Our results suggest a proportional increase in total drug release after repetitive laser irradiation. We hypothesize that the drug is released via “melted” lipid bilayers when the plasmonic materials on the liposome surface are heated by laser irradiation followed by reversible formation of the liposome. To evaluate our hypothesis, the number density of liposomes after laser irradiation was measured using single-particle (liposome) collision experiments at an ultramicroelectrode. Collisional frequency data suggest that the number density of liposomes remains unaltered even after 60 s of laser irradiation at 1.1 and 1.8 W, indicating that the liposome structure is reversible. The results were further compared with gold nanorod-coated nanodroplets where drug is released via irreversible phase transition. In contrast to what was observed with the liposome particles, the number density of the nanodroplets decreased with increasing laser irradiation duration. The structure reversibility of our liposome particles may be responsible for repetitive drug release with laser heating. We also studied the temperature rise in the lipid bilayer by incorporating polymerized 10,12-pentacosadiynoic acid (PCDA) in the lipid composition. The red shift in the UV–vis spectrum due to the structural change in PCDA lipids after laser irradiation indicates a rise in temperature above 75 °C, which is also above the chain-melting temperature of the main lipid used in the liposomes. All these results indicate that drug is released from the light-activatable liposomes due to reversible nanostructural alteration in the lipid bilayer by plasmonic resonance heating. The liposomes have potential to be a drug carrier for dose-controlled repetitive drug delivery.

中文翻译：

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激光辐照对可光活化药物包裹的脂质体的可逆性和药物释放的影响。

尽管一些研究表明使用可光激活的脂质体可重复释放药物，但每次激活时药物释放不一致会限制广泛使用。在这里，我们报告使用可逆的等离激元材料包衣的脂质体，用于通过反复激光照射按比例控制甲氨蝶呤（MTX）的递送，甲氨蝶呤是一种用于治疗癌症和自身免疫性疾病的常见药物。我们的结果表明，重复激光照射后总药物释放成比例增加。我们假设当通过激光照射加热脂质体表面上的等离子体材料，然后可逆地形成脂质体时，药物通过“融化”的脂质双层释放。为了评估我们的假设，在超微电极上使用单粒子（脂质体）碰撞实验测量激光照射后脂质体的数量密度。碰撞频率数据表明，即使在1.1和1.8 W的激光照射60 s后，脂质体的数量密度仍保持不变，表明脂质体的结构是可逆的。将该结果与金纳米棒包被的纳米液滴进一步比较，其中药物通过不可逆的相变释放。与脂质体颗粒观察到的相反，纳米液滴的数量密度随着激光照射持续时间的增加而降低。我们的脂质体颗粒的结构可逆性可能是由于激光加热导致药物重复释放的原因。我们还通过掺入聚合10来研究脂质双层的温升，脂质成分中的12-戊二醛酸（PCDA）。由于激光辐照后PCDA脂质的结构变化，UV-vis光谱出现红移，表明温度升高至75°C以上，该温度也高于脂质体中使用的主要脂质的链熔化温度。所有这些结果表明，由于等离子体共振加热使脂质双层中的可逆纳米结构改变，药物从可光活化脂质体中释放出来。脂质体有可能成为剂量控制重复药物递送的药物载体。该温度也高于脂质体中使用的主要脂质的链熔化温度。所有这些结果表明，由于等离子体共振加热使脂质双层中的可逆纳米结构改变，药物从可光活化脂质体中释放出来。脂质体有可能成为剂量控制重复药物递送的药物载体。该温度也高于脂质体中使用的主要脂质的链熔化温度。所有这些结果表明，由于等离子体共振加热使脂质双层中的可逆纳米结构改变，药物从可光活化脂质体中释放出来。脂质体有可能成为剂量控制重复药物递送的药物载体。