Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, People's Republic of China.
Department of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing 400038, People's Republic of China.
Nanotechnology. 2021 Mar 25;32(24). doi: 10.1088/1361-6528/abed03.
Targeted lipid nanobubbles as theranostic ultrasound molecular probes with both targeted contrast-enhanced ultrasound molecular imaging and synergistic treatment capabilities are expected to overcome severe challenges in the diagnosis and treatment of refractory triple-negative breast cancer (TNBC). In this study, AS1411 aptamer-functionalised nucleolin-targeted doxorubicin-loaded lipid nanobubbles (AS1411-DOX-NBs) were constructed, and their physicochemical properties as well as anti-tumour and cardioprotective efficacies were systematically tested and evaluated. The results showed that AS1411-DOX-NBs can carry and maintain the physicochemical and pharmacodynamic properties of doxorubicin (DOX) and show stronger tumour cell-killing abilityby increasing the active uptake of drugs. AS1411-DOX-NBs also significantly inhibited the growth of TNBC xenografts while maintaining the weight and health of the mice. Echocardiography and pathological examination further confirmed that AS1411-DOX-NBs effectively caused tumour tissue apoptosis and necrosis while reducing DOX-induced cardiotoxicity. The AS1411-DOX-NBs constructed in this study enable both targeted contrast-enhanced ultrasound molecular imaging and synergistic therapeutic efficacy and can be used as safe and efficient theranostic ultrasound molecular probes for the diagnosis and treatment of TNBC.
靶向脂质纳米气泡作为治疗性超声分子探针，具有靶向增强超声分子成像和协同治疗能力，有望克服三阴性乳腺癌（TNBC）诊断和治疗的严峻挑战。在本研究中，构建了 AS1411 适配体功能化核仁素靶向阿霉素载脂质纳米气泡（AS1411-DOX-NBs），并对其理化性质以及抗肿瘤和心脏保护疗效进行了系统的测试和评估。结果表明，AS1411-DOX-NBs 可以携带和维持阿霉素（DOX）的理化和药效学性质，并通过增加药物的主动摄取，表现出更强的肿瘤细胞杀伤能力。AS1411-DOX-NBs 还显著抑制了 TNBC 异种移植瘤的生长，同时保持了小鼠的体重和健康。超声心动图和病理检查进一步证实，AS1411-DOX-NBs 有效诱导肿瘤组织凋亡和坏死，同时减少 DOX 诱导的心脏毒性。本研究构建的 AS1411-DOX-NBs 既能实现靶向增强超声分子成像，又能发挥协同治疗效果，可作为安全有效的 TNBC 诊断和治疗的治疗性超声分子探针。
