Catania Rosa, Onion David, Russo Emanuele, Zelzer Mischa, Mantovani Giuseppe, Huett Alan, Stolnik Snow
School of Pharmacy, University of Nottingham Nottingham NG7 2RD UK
School of Life Sciences, University of Nottingham Nottingham NG7 2UH UK.
RSC Adv. 2022 Jun 6;12(26):16561-16569. doi: 10.1039/d2ra02307e. eCollection 2022 Jun 1.
Control over intracellular release of therapeutic compounds incorporated into nano-carriers will open new possibilities for targeted treatments of various diseases including cancer, and viral and bacterial infections. Here we report our study on mechanoresponsive nano-sized liposomes which, following internalization by cells, achieve intracellular delivery of encapsulated cargo on application of external ultrasound stimulus. This is demonstrated in a bespoke cell reporter system designed to assess free drug in cytoplasm. Biophysical analyses show that drug release is attributable to the action of a mechanoresponsive spiropyran-based compound embedded in the liposomal lipid membrane. Exposure to external ultrasound stimulus results in opening of the molecular structure of the embedded spiropyran, a consequent increase in liposomal lipid membrane fluidity, and size-dependent release of encapsulated model drugs, all pointing to lipid bilayer perturbation. The study hence illustrates feasibility of the proposed concept where intracellular drug release from mechanoresponsive liposomes can be triggered on demand by external ultrasound stimulus.
控制纳入纳米载体的治疗性化合物的细胞内释放，将为包括癌症、病毒和细菌感染在内的各种疾病的靶向治疗开辟新的可能性。在此，我们报告了对机械响应性纳米脂质体的研究，这些脂质体在被细胞内化后，在外部超声刺激下实现了封装货物的细胞内递送。这在一个专门设计用于评估细胞质中游离药物的细胞报告系统中得到了证明。生物物理分析表明，药物释放归因于嵌入脂质体脂质膜中的基于机械响应性螺吡喃的化合物的作用。暴露于外部超声刺激会导致嵌入的螺吡喃分子结构打开，进而导致脂质体脂质膜流动性增加，以及封装的模型药物的尺寸依赖性释放，所有这些都表明脂质双层受到扰动。因此，该研究说明了所提出概念的可行性，即通过外部超声刺激可以按需触发机械响应性脂质体的细胞内药物释放。
