Intracellular Breakable and Ultrasound‐Responsive Hybrid Microsized Containers for Selective Drug Release into Cancerous Cells

• Published in: Particle & particle systems characterization 2017-05, Vol.34 (5), p.1600417-n/a
• Main Authors: Timin, Alexander S., Muslimov, Albert R., Lepik, Kirill V., Okilova, Maria V., Tcvetkov, Nikolai Y., Shakirova, Alena I., Afanasyev, Boris V., Gorin, Dmitry A., Sukhorukov, Gleb B.
• Format: Article
• Language: English
• Subjects: cancer therapy; intracellular degradation; multiresponsive triggering; polyelectrolyte capsules; sol‐gel methods; ultrasound
• ISSN: 0934-0866; 1521-4117
• DOI: 10.1002/ppsc.201600417

This work reports an efficient and straightforward strategy to fabricate hybrid microsized containers with reduction‐sensitive and ultrasound‐responsive properties. The ultrasound and reductive sensitivity are visualized using scanning electron microscopy, with the results showing structural decomposition upon ultrasound irradiation and in the presence of reducing agent. The ultrasound‐responsive functionalities of hybrid carriers can be used as external trigger for rapid controlled release, while prolonged drug release can be achieved in the presence of reducing agent. To evaluate the potential for targeted drug delivery, hybrid microsized containers are loaded with the anticancer drug doxorubicin (Dox). Such hybrid capsules can undergo structural intracellular degradation after cellular uptake by human cervical cancer cell line (HeLa), resulting in Dox release into cancer cells. In contrast, there is no Dox release when hybrid capsules are incubated with human mesenchymal stem cells (MSCs) as an example of normal human cells. The cell viability results indicate that Dox‐loaded capsules effectively killed HeLa cells, while they have lower cytotoxicity against MSCs as an example of healthy cells. Thus, the newly developed intracellular‐ and ultrasound‐responsive microcarriers obtained via sol‐gel method and layer‐by‐layer technique provide a high therapeutic efficacy for cancer, while minimizing adverse side effect. Comparative analysis of stimuli‐responsive drug release into mesenchymal stem cells as an example of healthy cells and cancerous cells is performed using a novel type of dual‐responsive microsized containers made of assembled polyelectrolytes followed up by in situ sol–gel coating.