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Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment.

ABSTRACT: The development of novel anticancer therapies warrants the parallel development of biomarkers that can quantify their effectiveness. Photoacoustic imaging has the potential to measure changes in tumor vasculature during treatment. Establishing the accuracy of imaging biomarkers requires direct comparisons with gold histological standards. In this work, we explore whether a new class of submicron, vascular disrupting, ultrasonically stimulated nanobubbles enhance radiation therapy. In vivo experiments were conducted on mice bearing prostate cancer tumors. Combined nanobubble plus radiation treatments were compared against conventional microbubbles and radiation alone (single 8?Gy fraction). Acoustic resolution photoacoustic imaging was used to monitor the effects of the treatments 2- and 24-hs post-administration. Histological examination provided metrics of tumor vascularity and tumoral cell death, both of which were compared to photoacoustic-derived biomarkers. Photoacoustic metrics of oxygen saturation reveal a 20 % decrease in oxygenation within 24?h post-treatment. The spectral slope metric could separate the response of the nanobubble treatments from the microbubble counterparts. This study shows that histopathological assessment correlated well with photoacoustic biomarkers of treatment response.

SUBMITTER: Hysi E

PROVIDER: S-EPMC7393572 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment.

Hysi Eno E Fadhel Muhannad N MN Wang Yanjie Y Sebastian Joseph A JA Giles Anoja A Czarnota Gregory J GJ Exner Agata A AA Kolios Michael C MC

Photoacoustics 20200725

The development of novel anticancer therapies warrants the parallel development of biomarkers that can quantify their effectiveness. Photoacoustic imaging has the potential to measure changes in tumor vasculature during treatment. Establishing the accuracy of imaging biomarkers requires direct comparisons with gold histological standards. In this work, we explore whether a new class of submicron, vascular disrupting, ultrasonically stimulated nanobubbles enhance radiation therapy. <i>In vivo</i> ...[more]

PMID: 32775198

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Project description:Molecular photoacoustic imaging (PA) is a promising technology to understand tumor pathology and guide precision therapeutics. Despite the capability of activatable PA probes to image tumor-specific biomarkers, limitations in their molecular structure hamper them from effective drug delivery and the drug release monitoring. Herein, we developed a perylene diimide (PDI) based theranostic platform that provides noninvasive PA imaging signals to monitor tumor-specific pH-responsive drug release. Methods: we first designed and synthesized an acid-responsive amine-substituted PDI derivative. The pH sensitive properties of the PDI was demonstrated by density functional theory (DFT) calculations, UV-vis experiments and PA studies. The theranostic platform (THPDINs) was fabricated by self-assembly of the acid-responsive PDI, a pH irrelevant IR825 dye, and anti-cancer drug doxorubicin (DOX). The PA properties in various pH environment, drug delivery, cytotoxicity, cell uptake, ratiometric PA imaging and anti-tumor efficacy of the THPDINs were investigated in vitro and in vivo by using U87MG glioma cell line and U87MG tumor model. Results: We found that our designed PDI was sensitive to the tumor specific pH environment, reflected by absorbance shift, PA intensity and aggregation morphology changes in aqueous solution. The as-synthesized pH sensitive PDI acted as a molecular switch in the THPDINs, in which the switch can be triggered in the mild acidic tumor microenvironment to accelerate DOX release. Meanwhile, the DOX release could be monitored by ratiometric PA imaging. Conclusions: We developed a multifunctional PDI based theranostic platform for noninvasive real-time ratiometric PA imaging of tumor acidic pH and monitoring of drug release in living mice simultaneously. This strategy will shed light on the development of smart activatable theranostic nanoplatforms and will significantly advance the application of PA theranostics in biology and medicine.

Dataset Information

Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment.

Publications

Photoacoustic imaging biomarkers for monitoring biophysical changes during nanobubble-mediated radiation treatment.

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