Multifunctional nanostructured drug delivery carriers for cancer therapy: Multimodal imaging and ultrasound-induced drug release

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2021-04, Vol.200, p.111576-111576, Article 111576
• Main Authors: Novoselova, Marina V., German, Sergei V., Abakumova, Tatiana O., Perevoschikov, Stanislav V., Sergeeva, Olga V., Nesterchuk, Mikhail V., Efimova, Olga I., Petrov, Kirill S., Chernyshev, Vasiliy S., Zatsepin, Timofei S., Gorin, Dmitry A.
• Format: Article
• Language: English
• Subjects: Biodistribution; Capsules; Drug delivery; Fluorescent tomography; Layer-By-Layer encapsulation; MRI; Nanomedicine; Photoacoustics; Ultrasound-induced release
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2021.111576

[Display omitted] •Freezing induced loading and Layer by Layer methods were used for contrast agent preparation.•Multifunctional contrast agents, which includes doxorubicin and MNP, can be detected by MRI, FT, and PA systems.•The destruction of capsules was investigated using MRI, FT, and PA systems.•Fast time- and site-specific release of Cy7 and doxorubicin in vivo under HIFU was demonstrated. Development of multimodal systems for therapy and diagnosis of neoplastic diseases is an unmet need in oncology. The possibility of simultaneous diagnostics, monitoring, and therapy of various diseases allows expanding the applicability of modern systems for drug delivery. We have developed hybrid particles based on biocompatible polymers containing magnetic nanoparticles (MNPs), photoacoustic (MNPs), fluorescent (Cy5 or Cy7 dyes), and therapeutic components (doxorubicin). To achieve high loading efficiency of MNP and Dox to nanostructured carriers, we utilized a novel freezing-induced loading technique. To reduce the systemic toxicity of antitumor drugs and increase their therapeutic efficacy, we can use targeted delivery followed by the remote control of drug release using high intensity-focused ultrasound (HIFU). Loading of MNPs allowed performing magnetic targeting of the carriers and enhanced optoacoustic signal after controlled destruction of the shell and release of therapeutics as well as MRI imaging. The raster scanning optoacoustic mesoscopy (PA, RSOM), MRI, and fluorescent tomography (FT) confirmed the ultrasound-induced release of doxorubicin from capsules: in vitro (in tubes and pieces of meat) and in vivo (after delivery to the liver). Disruption of capsules results in a significant increase of doxorubicin and Cy7 fluorescence initially quenched by magnetite nanoparticles that can be used for real-time monitoring of drug release in vivo. In addition, we explicitly studied cytotoxicity, intracellular localization, and biodistribution of these particles. Elaborated drug delivery carriers have a good perspective for simultaneous imaging and focal therapy of different cancer types, including liver cancer.