Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer

Abstract

Background Tumor cell-derived exosomes (TEx) have emerged as promising nanocarriers for drug delivery. Noninvasive multimodality imaging for tracing the in vivo trafficking of TEx may accelerate their clinical translation. In this study, we developed a TEx-based nanoprobe via hydrophobic insertion mechanism and evaluated its performance in dual single-photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) imaging of colon cancer. Results TEx were successfully isolated from HCT116 supernatants, and their membrane vesicle structure was confirmed by TEM. The average hydrodynamic diameter and zeta potential of TEx were 110.87 ± 4.61 nm and –9.20 ± 0.41 mV, respectively. Confocal microscopy and flow cytometry findings confirmed the high tumor binding ability of TEx. The uptake rate of 99mTc-TEx-Cy7 by HCT116 cells increased over time, reaching 14.07 ± 1.31% at 6 h of co-incubation. NIRF and SPECT imaging indicated that the most appropriate imaging time was 18 h after the injection of 99mTc-TEx-Cy7 when the tumor uptake (1.46% ± 0.06% ID/g) and tumor-to-muscle ratio (8.22 ± 0.65) peaked. Compared with radiolabeled adipose stem cell derived exosomes (99mTc-AEx-Cy7), 99mTc-TEx-Cy7 exhibited a significantly higher tumor accumulation in tumor-bearing mice. Conclusion Hydrophobic insertion-based engineering of TEx may represent a promising approach to develop and label exosomes for use as nanoprobes in dual SPECT/NIRF imaging. Our findings confirmed that TEx has a higher tumor-targeting ability than AEx and highlight the potential usefulness of exosomes in biomedical applications.

Cell membrane camouflaged biomimetic nanoparticles: Focusing on tumor theranostics

“…Jing et al. [ 142 ] developed an exosome-based NPs ( 99m Tc-Tex-Cy7) via the hydrophobic effect introduced encapsulation mechanism for SPECT and NIR imaging in colon cancer ( Fig. 3 ).…”

Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma

“…Under both physiological and pathological conditions, SEVs mediate the exchange of information between cells and their surroundings [ 145 – 149 ]. TEXs have emerged as a major communication mechanism between tumor cells and TMEs and have a vital role in tumor progression and metastasis [ 11 , 150 – 154 ]. The application of TEXs in the diagnosis and treatment of glioma is still in the nascent stages.…”

Recent advances in targeted drug delivery systems for resistant colorectal cancer

“…Lan et al exploited exosome as theranostics for simultaneous CRC therapy and imaging. In this case, exosomes were extracted from tumor cells, and were labeled with radionucleutide and Cy5 to create multimodality imaging probe which target the CRC cells efficiently through single-photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) imaging of colon cancer in mice [ 100 ]. Not to forget exosomal miRNA applications in diagnosis, prognosis and treatment of CRC.…”