State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Int J Nanomedicine. 2021 Jul 6;16:4643-4659. doi: 10.2147/IJN.S315650. eCollection 2021.
Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.
We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF . Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.
The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects.
We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.
缺氧被认为对肿瘤治疗有阻碍作用，但低氧环境为（BF）定植提供了适宜的栖息地。由于其对肿瘤核心缺氧的偏好，厌氧菌 BF 经全身注射后会选择性地定植于肿瘤中。因此，BF 可能是一种潜在的靶向药物，可有效地用于肿瘤治疗。我们旨在确定一种新的 BF 介导的策略，即通过适体靶向方法将 AP-PFH/PLGA NPs（适体 CCFM641-5 功能化全氟己烷（PFH）负载聚乳酸-共-羟基乙酸（PLGA）纳米粒）递送至基于 BF 的实体瘤中，是否可以提高高强度聚焦超声（HIFU）治疗乳腺癌的效率。
我们使用双重乳液法和碳二亚胺法合成了 AP-PFH/PLGA NPs。然后，我们评估了 AP-PFH/PLGA NPs 对 BF 的靶向能力。最后，我们研究了基于 BF 加 AP-PFH/PLGA NPs（BF 介导的 HIFU 消融）的 HIFU 消融的疗效。
精心设计的 AP-PFH/PLGA NPs 可以靶向 BF 定植于肿瘤，实现高肿瘤蓄积，从而显著增强 HIFU 的治疗效果。我们还发现，与传统化疗相比，这种治疗不仅抑制肿瘤生长，而且显著延长了小鼠的生存时间。更重要的是，这种治疗策略没有明显的副作用。
我们成功建立了一种新的治疗方法，即 BF 介导的 HIFU 消融，为高效、非侵入性的肿瘤治疗提供了一个极好的平台。
