CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors

Abstract

PurposeTargeted nanobubbles can penetrate the tumor vasculature and achieve ultrasound molecular imaging (USMI) of tumor parenchymal cells. However, most targeted nanobubbles only achieve USMI of tumor parenchymal cells from one organ, and their distribution, loading ability, and binding ability in tumors are not clear. Therefore, targeted nanobubbles loaded with carbonic anhydrase IX (CAIX) aptamer were fabricated for USMI of various tumors, and the morphological basis of USMI with targeted nanobubbles was investigated.Materials and methodsThe specificity of CAIX aptamer at the cellular level was measured by immunofluorescence and flow cytometry. Targeted nanobubbles loaded with CAIX aptamer were prepared by a maleimidethiol coupling reaction, and their binding ability to CAIX-positive tumor cells was analyzed in vitro. USMI of targeted and non-targeted nanobubbles was performed in tumor-bearing nude mice. The distribution, loading ability, and binding ability of targeted nanobubbles in xenograft tumor tissues were demonstrated by immunofluorescence.ResultsCAIX aptamer could specifically bind to CAIX-positive 786-O and Hela cells, rather than CAIX-negative BxPC-3 cells. Targeted nanobubbles loaded with CAIX aptamer had the advantages of small size, uniform distribution, regular shape, and high safety, and they could specifically accumulate around 786-O and Hela cells, while not binding to BxPC-3 cells in vitro. Targeted nanobubbles had significantly higher peak intensity and larger area under the curve than non-targeted nanobubbles in 786-O and Hela xenograft tumor tissues, while there was no significant difference in the imaging effects of targeted and non-targeted nanobubbles in BxPC-3 xenograft tumor tissues. Immunofluorescence demonstrated targeted nanobubbles could still load CAIX aptamer after penetrating the tumor vasculature and specifically binding to CAIX-positive tumor cells in xenograft tumor tissues.ConclusionTargeted nanobubbles loaded with CAIX aptamer have a good imaging effect in USMI of tumor parenchymal cells, and can improve the accuracy of early diagnosis of malignant tumors from various organs.

Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and Treatment of Prostate Cancer

“…Liposomes have the advantages of good biocompatibility, simple preparation process, fewer toxic and side effects, and are widely used in gene transfection, drug delivery and in vivo imaging [19]. Our previous findings and other related studies have shown that nanobubbles with a lipid shell have the characteristics of entering tumor tissues through tumor blood vessels and concentrating therein for a long time [20]. At the same time, ultrasound targeted nanobubble destruction (UTND) provides an effective way to direct drugs to specific parts of the body; effectively increasing the content of the drug in the tumor area and reducing potential side effects, thereby contributing effectively to the treatment of the tumors.…”

Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and the Treatment of Prostate Cancer

“…Liposomes have the advantages of good biocompatibility, a simple preparation process, and fewer toxic effects and side effects and are widely used in gene transfection, drug delivery and in vivo imaging [21]. Our previous ndings and other related studies have shown that nanobubbles with a lipid shell can enter tumour tissues through tumour blood vessels and concentrate therein for a long period of time [22]. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to direct drugs to speci c parts of the body, effectively increasing the drug content in the tumour area and reducing potential side effects, thereby contributing effectively to the treatment of tumours.…”

Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management

“…Another diagnostic approach employs ultrasound molecular imaging (USMI), using CAIX-targeted bubbles, allowing the detection of masses that express the marker. Facility, accessibility and innocuity are solid arguments for this technique [ 41 ]. Table 2 summarizes the evidence on the clinical value of CAIX targeting in molecular imaging.…”

“…Zhu et al described a new USMI contrast product: CAIX aptamer-functionalized targeted nanobubbles [ 41 ]. As seen above, CAIX may be expressed by many different malignancies and it is a trans-membranous protein.…”