Li Jianping, Ji Hong, Jing Yong, Wang Shiguang
Department of Geriatric Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610041, Sichuan, China.
Department of Imaging, Eastern Hospital of Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610000, Sichuan, China.
Nanoscale Res Lett. 2020 Feb 3;15(1):31. doi: 10.1186/s11671-020-3252-z.
In this study, we developed a multifunctional ultrasound (US) therapeutic agent that encapsulates perfluoropentane (PFP) into ferritin (FRT) and conjugates the tumor-targeting molecule folic acid (FA) (FA-FRT-PFP). The prepared FA-FRT-PFP had an average particle diameter of 42.8 ± 2.5 nm, a zeta potential of - 41.1 ± 1.7 mV and shows good stability in physiological solution and temperatures. FRT is a pH-sensitive cage protein that, at pH 5.0, disassembles to form pores that can load PFP. The adjustment to neutral pH closes the pores and encapsulates the PFP inside the FRT to form nanoparticles. At pH 5.0, 3 min of low-intensity focused ultrasound (LIFU, 2 W/cm) significantly enhanced the US signal of FA-FRT-PFP through the acoustic droplet vaporization (ADV) effect. Under identical conditions, 4 min of LIFU irradiation caused the bubbles generated by FA-FRT-PFP to break. FA-FRT-PFP could be efficiently targeted into ovarian cancer cells and significantly enhanced the US contrast of FA-FRT-PFP after 3 min of LIFU irradiation. After 4 min of LIFU irradiation, cell viability significantly decreased due to necrosis, likely due to the FA-FRT-PFP mediated release of PFP in the acidic environment of lysosomes after entering the tumor cells. PFP is then transformed into bubbles that burst under LIFU irradiation, forming physical shock waves that lead to the destruction of the cell structure and necrosis, achieving tumor treatment. Taken together, this demonstrates that FA-FRT-PFP is both a novel and promising US theranostics agent for future clinic application.
在本研究中，我们开发了一种多功能超声（US）治疗剂，该治疗剂将全氟戊烷（PFP）封装到铁蛋白（FRT）中，并偶联肿瘤靶向分子叶酸（FA）（FA-FRT-PFP）。制备的FA-FRT-PFP平均粒径为42.8±2.5nm，zeta电位为-41.1±1.7mV，在生理溶液和温度下表现出良好的稳定性。FRT是一种对pH敏感的笼形蛋白，在pH 5.0时会分解形成可装载PFP的孔。将pH调节至中性会关闭孔，并将PFP封装在FRT内部以形成纳米颗粒。在pH 5.0时，3分钟的低强度聚焦超声（LIFU，2W/cm）通过声滴汽化（ADV）效应显著增强了FA-FRT-PFP的超声信号。在相同条件下，4分钟的LIFU照射会导致FA-FRT-PFP产生的气泡破裂。FA-FRT-PFP可以有效地靶向进入卵巢癌细胞，并在3分钟的LIFU照射后显著增强FA-FRT-PFP的超声对比度。在4分钟的LIFU照射后，细胞活力因坏死而显著降低，这可能是由于FA-FRT-PFP在进入肿瘤细胞后在溶酶体的酸性环境中介导PFP释放所致。然后PFP转化为气泡，在LIFU照射下破裂，形成物理冲击波，导致细胞结构破坏和坏死，从而实现肿瘤治疗。综上所述，这表明FA-FRT-PFP是一种新型且有前景的用于未来临床应用的超声诊疗剂。
