靶特异性药物释放对于提高化疗疗效是必不可少的,因为它增强了药物摄取和渗透到肿瘤中。声响应性载药纳米/微米颗粒是通过将它们暴露于肿瘤附近的超声来实现目标特异性的有前途的解决方案。然而,复杂的合成过程和有限的超声(美国)暴露条件,如超声聚焦深度和声功率的有限控制,防止这种方法在临床实践中的实际应用。这里,我们提出了一个凸声透镜附着的美国(CALUS)作为一个简单的,经济,和有效的替代集中的美国药物递送系统(DDS)的应用。使用水听器对CALUS进行了数值和实验表征。体外,使用具有各种声学参数的CALUS破坏微流体通道内的微气泡(MB)(声压[P],脉冲重复频率[PRF],和占空比)和流速。在体内,通过表征肿瘤生长速率,使用携带黑色素瘤的小鼠评估肿瘤抑制,动物体重,和有/没有CALUSDDS的肿瘤内药物浓度。美国光束被测量为由CALUS有效会聚,这与我们的模拟结果一致。通过CALUS诱导的MB破坏试验对声学参数进行了优化(P=2.34MPa,PRF=100kHz,和占空比=9%);此最佳参数组合成功地诱导了微流体通道内MB的破坏,平均流速高达9.6cm/s。CALUS还增强了抗肿瘤药物(多柔比星)在鼠黑素瘤模型中的体内治疗效果。多柔比星和CALUS的组合比单独的多柔比星抑制肿瘤生长〜55%,清楚地表明协同抗肿瘤功效。我们的肿瘤生长抑制性能优于其他基于药物载体的方法,即使没有耗时和复杂的化学合成过程。这个结果表明我们的小说,简单,经济,和有效的目标特异性DDS可能提供从临床前研究到临床试验的过渡和潜在的治疗方法为以患者为中心的医疗保健。
Target-specific drug release is indispensable to improve chemotherapeutic efficacy as it enhances drug uptake and penetration into tumors. Sono-responsive drug-loaded nano-/micro-particles are a promising solution for achieving target specificity by exposing them to ultrasound near tumors. However, the complicated synthetic processes and limited ultrasound (US) exposure conditions, such as limited control of ultrasound focal depth and acoustic power, prevent the practical application of this approach in clinical practice. Here, we propose a convex acoustic lens-attached US (CALUS) as a simple, economic, and efficient alternative of focused US for drug delivery system (DDS) application. The CALUS was characterized both numerically and experimentally using a hydrophone. In vitro, microbubbles (MBs) inside microfluidic channels were destroyed using the CALUS with various acoustic parameters (acoustic pressure [P], pulse repetition frequency [PRF], and duty cycle) and flow velocity. In vivo, tumor inhibition was evaluated using melanoma-bearing mice by characterizing tumor growth rate, animal weight, and intratumoral drug concentration with/without CALUS DDS. US beams were measured to be efficiently converged by CALUS, which was consistent with our simulation results. The acoustic parameters were optimized through the CALUS-induced MB destruction test (P = 2.34 MPa, PRF = 100 kHz, and duty cycle = 9%); this optimal parameter combination successfully induced MB destruction inside the microfluidic channel with an average flow velocity of up to 9.6 cm/s. The CALUS also enhanced the therapeutic effects of an antitumor drug (doxorubicin) in vivo in a murine melanoma model. The combination of the doxorubicin and the CALUS inhibited tumor growth by ∼ 55% more than doxorubicin alone, clearly indicating synergistic antitumor efficacy. Our tumor growth inhibition performance was better than other methods based on drug carriers, even without a time-consuming and complicated chemical synthesis process. This result suggests that our novel, simple, economic, and efficient target-specific DDS may offer a transition from preclinical research to clinical trials and a potential treatment approach for patient-centered healthcare.