An Activatable Hybrid Organic–Inorganic Nanocomposite as Early Evaluation System of Therapy Effect

Abstract

Delays in evaluating cancer response to radiotherapy (RT) usually reduce therapy effect or miss the right time for treatment optimization. Hence, exploring timely and accurate methods enabling one to gain insights of RT response are highly desirable. In this study, we have developed an apoptosis enzyme (caspase-3) activated nanoprobe for early evaluation of RT efficacy. The nanoprobe bridged the nanogapped gold nanoparticles (AuNNPs) and the second near-infrared window (NIR-II) fluorescent (FL) molecules (IR-1048) through a caspase-3 specific peptide sequence (DEVD) (AuNNP@DEVD-IR1048). After X-ray irradiation, caspase-3 was activated to cut DEVD, turning on both NIR-II FL and PA imaging signals. The increased NIR-II FL/PA signals exhibited a positive correlation with the content of caspase-3. Moreover, the amount of the activated caspase-3 was negatively correlated with the tumor size. The results underscore the role of the caspase-3 activated by X-ray irradiation in bridging the imaging signals variation and tumor inhibition rate. Overall, activatable NIR-II FL/PA imaging was successfully used to timely predict and evaluate the RT efficacy. The evaluation system based on biomarkertriggered living imaging has the capacity to guide treatment decisions for numerous cancer types.

An Activatable Polymeric Nanoprobe for Fluorescence and Photoacoustic Imaging of Tumor‐Associated Neutrophils in Cancer Immunotherapy

“…[10] Activatable PA imaging probes that only trigger the signals in the presence of specific molecular biomarkers offer measurable and quantifiable information on physiological and pathological status at the molecular level. [11] Among many PA agents including gold nanoparticles, [12] carbon-based nanomaterials, [13] hemicyanine, [14] and dye-containing nanoparticles, [15] semiconducting polymer nanoparticles (SPNs) exhibit structural versatility for the design of activatable PA imaging probes. [16] Till now, activatable PA probes have been extensively investigated for in vivo imaging of a variety of biologically active metabolites and disease-specific biomarkers, including aberrant pH, [17] ROS, [18] glutathione, [19] metal ions, [20] overexpression of enzymes.…”

Nanomedicine embraces cancer radio-immunotherapy: mechanism, design, recent advances, and clinical translation

“…Because of a relatively slow therapeutic response towards radiotherapy and immunotherapy due to changes in tumor size, invasion, and metastasis, this nanomedicine-mediated approach can unveil timely, accurate and specific information about tumor tissues after RT treatment, such as dynamic changes in immune cell infiltration and early indicators (e.g., elevated ROS or caspase-3). 258,282 Circulating tumor DNA (ctDNA) acts an early evaluation indicator for in vitro diagnosis and provides valuable prognostic information about patients treated with antitumor immunotherapy and/or radiotherapy. 283,284 A feasible approach for the in vitro detection of ctDNA could be the use of nanomedicine-aided detection probes, such as gold nanoparticles and DNA nanomedicines.…”

Activatable Multimodal Probes for In Vivo Imaging and Theranostics

“…FL imaging in the second near‐infrared window (NIR‐II, 1000–1700 nm) offers lower light scattering and auto‐fluorescence compared to FL imaging in the first NIR window (NIR‐I, 650–950 nm), which allows for deeper penetration depth and lower background signals than NIR‐I FL imaging [34] . Very recently, Song and co‐workers developed a caspase‐3 activatable NIR‐II FL/PA bimodal nanoprobe ( AuNNP@DEVD‐IR1048 ) by conjugating an NIR‐II fluorophore (IR1048) to core–shell structured gold nanoparticles (AuNNPs) through the caspase‐3‐cleavable peptide substrate (DEVD) [35] . Moreover, a pair of cyanobenzothiazole (CBT) and Cys residues capable of proceeding through rapid condensation reactions [36] were also covalently linked to the AuNNPs.…”