DNA-based nanocarriers to enhance the optoacoustic contrast of tumorsin vivo

Abstract

Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near infrared dyes to enhance contrast at the tumor site. While these agents afford excellent biocompatibility and minimal toxicity, they present limited optoacoustic signal generation capability and rapid renal clearance, which can impede their tumor imaging efficacy. In this work, a synthetic strategy to overcome these limitations utilizing biodegradable DNA-based nanocarrier (DNA-NC) platforms is introduced. DNA-NCs enable the incorporation of near infrared dyes (in this case, IRDye 800CW) at precise positions to enable fluorescence quenching and maximize optoacoustic signal generation. Furthermore, these DNA-NCs show a prolonged blood circulation compared to the native fluorophores, facilitating tumor accumulation by the Enhanced Permeability and Retention (EPR) effect. In vivo imaging of tumor xenografts in mice following intravenous administration of DNA-NCs revealed enhanced OT signals at 24h when compared to free fluorophores, indicating promise for this method to enhance the optoacoustic signal generation capability and tumor uptake of clinically relevant near infrared dyes.

DNA-Liposome Hybrid Carriers for Triggered Cargo Release

“…To address these challenges, the development of larger carrier constructs has shown promise, especially if these are targeted. [3][4][5][6] Thus, the encapsulation of small therapeutic molecules by carrier structures holds great potential to maximize delivery efficiency. To fulfil a therapeutic effect, however, the drug must become bioavailable by being released from the carrier.…”

Multimodal Contrast Agents for Optoacoustic Brain Imaging in Small Animals

“…NIR II probes allow for deeper penetration, improved signal/noise ratio, and more reliable unmixing from strong endogenous hemoglobin background. Many NIR II OA/fluorescence probes, such as novel NIR II OA probes with DNA-based nanocarriers, PEGylated Au nanoparticles, and SPNs, that are of high chemical stability, low toxicity, and a high signal-to-noise ratio showed great promise for multimodal imaging and photothermal therapy ( Jin et al, 2010 ; Ding et al, 2019 ; Meng et al, 2019 ; Sun et al, 2019 ; Zhang et al, 2019c ; Feng et al, 2020 ; Xu et al, 2020 ; Joseph et al, 2021 ; Miyasato et al, 2021 ). 5) Toward clinical translation: For fluorescence imaging, the U.S. Food and Drug Administration (FDA) approved several probes such as ICG ( Mokrousov et al, 2021 ), methylene blue, fluorescein, Prussian blue, 5-aminolevulinic acid ( Stummer et al, 2006 ), and Evans blue.…”

“…The NPs utilized for OA imaging are mainly carbon-based NPs, for example, single-walled carbon nanotubes; metal-based NPs, for example, gold NPs; bismuth-based NPs; polymer-encapsulated organic NPs; semiconducting polymer NPs (SPNs); conjugated polymer; and novel DNA-based nanocarriers. ( Pu et al, 2014 ; Li and Chen, 2015 ; Weber et al, 2016 ; Yang et al, 2018 ; Yu et al, 2019 ; Zhan et al, 2019 ; Xu et al, 2020 ; Cheng et al, 2021 ; Fan et al, 2021 ; Joseph et al, 2021 ; Qi et al, 2021a ; Tuo et al, 2021 ; Wang et al, 2021a ; Wang et al, 2021b ; Zhen et al, 2021 ). NPs have the advantage of versatile multimodal imaging capacity, a favorable signal/noise ratio, high photothermal conversion, deep penetration depth with near-infrared (NIR) II probes, and diverse structure and types (activable, turnable, and metabolizable).…”

DNA-Liposome Hybrid Carriers for Triggered Cargo Release

“…To address these challenges, the development of larger carrier constructs has shown promise, especially if these are targeted. [3][4][5][6] Thus, the encapsulation of small therapeutic molecules by carrier structures holds great potential to maximize delivery efficiency. To fulfil a therapeutic effect, however, the drug must become bioavailable by being released from the carrier.…”