4.5 Article

Focused ultrasound-mediated sonochemical internalization: an alternative to light-based therapies

Journal

JOURNAL OF BIOMEDICAL OPTICS
Volume 21, Issue 7, Pages -

Publisher

SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
DOI: 10.1117/1.JBO.21.7.078002

Keywords

chemotherapy; bleomycin; photochemical internalization; sonochemical internalization; glioma therapy; endosomal escape

Funding

  1. Norwegian Radium Hospital Research Foundation
  2. LAMMP Program [NIBIB P41EB015890]
  3. Tony and Renee Marlon Charitable Foundation

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Activation of sonosensitizers via focused ultrasound (FUS), i.e., sonodynamic therapy has been proposed as an extension to light-activated photodynamic therapy for the treatment of brain as well as other tumors. The use of FUS, as opposed to light, allows treatment to tumor sites buried deep within tissues as well as through the intact skull. We have examined ultrasonic activation of sonosensitizers together with the anticancer agent bleomycin (BLM), i.e., sonochemical internalization (SCI). SCI is a technique that utilizes FUS for the enhanced delivery of endo-lysosomal trapped macromolecules into the cell cytoplasm in a similar manner to light-based photochemical internalization. The released agent can, therefore, exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Our results indicate that, compared to drug or FUS treatment alone, FUS activation of the sonosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to grow as three-dimensional tumor spheroids in vitro. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)

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