Department of Ultrasonography, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Hainan, People's Republic of China.
Int J Nanomedicine. 2022 Oct 18;17:4879-4894. doi: 10.2147/IJN.S377514. eCollection 2022.
Chemotherapy is an important approach to treating nasopharyngeal carcinoma (NPC). Unfortunately, the lack of selectivity, insufficient tumor accumulation, uneven tumor distribution and severe systemic toxicity lead to the unsatisfactory performance of these drugs. While a more precise drug delivery, on-demand drug release, and deep diffusion of drugs (homogeneous distribution of drugs in the tumor) could improve the application, they remain challenging. Chemotherapeutic drug-loaded acoustic nanodroplet with dual-imaging capacity is expected to solve these problems.
Folate (Fa)-modified and doxorubicin (Dox)-loaded acoustic poly (lactic-co-glycolic acid) (PLGA), low intensity focused ultrasound (LIFU)-responsive perfluoropentane (PFP) and FeO nanoparticles (designated as Fa-Fe@P-PFP-Dox) were integrated by a double-emulsion method. After the synthesis, the LIFU-triggered acoustic droplet vaporization (ADV) effect, LIFU-triggered drug release, cell targeting capability, in vitro cell-killing effects, biodistribution, PA/MR dual imaging (PA: photoacoustic; MR: magnetic resonance), LIFU-augmented Dox distribution in tumors and chemotherapeutic efficacy of Fa-Fe@P-PFP-Dox were investigated.
The distribution of these drug-loaded nanodroplets was clearly monitored via PA/MR dual imaging. Upon LIFU irradiation, PFP within the Fa-Fe@P-PFP-Dox nanodroplets underwent ADV, which led to the release of Dox and promoted the deep penetration of Dox in tumor tissue, eventually achieving highly efficient chemotherapy against NPC. As a result, LIFU-triggered chemotherapy exerted a highly efficient therapeutic effect with a tumor inhibition rate of 74.24 ± 7.95%.
Fa-modified and drug-loaded acoustic nanodroplets have been successfully constructed for dual-imaging guided highly efficient chemotherapy against NPC. This novel tumor drug delivery method is expected to provide an efficient, visualized, and precise personalized treatment method for NPC patients with minimal side effects.
化疗是治疗鼻咽癌（NPC）的重要方法。然而，这些药物缺乏选择性、肿瘤蓄积不足、肿瘤分布不均匀以及严重的全身毒性，导致其疗效不尽如人意。更精确的药物输送、按需药物释放和药物的深层扩散（药物在肿瘤中的均匀分布）可以改善其应用，但仍然具有挑战性。具有双重成像能力的载化疗药物声纳米液滴有望解决这些问题。
采用双乳液法将叶酸（Fa）修饰和阿霉素（Dox）负载的声聚乳酸-羟基乙酸共聚物（PLGA）、低强度聚焦超声（LIFU）响应的全氟戊烷（PFP）和 FeO 纳米粒子（命名为 Fa-Fe@P-PFP-Dox）整合在一起。合成后，考察了 LIFU 触发的声滴蒸发（ADV）效应、LIFU 触发的药物释放、细胞靶向能力、体外细胞杀伤作用、生物分布、PA/MR 双重成像（PA：光声；MR：磁共振）、LIFU 增强的 Dox 在肿瘤中的分布以及 Fa-Fe@P-PFP-Dox 的化疗效果。
通过 PA/MR 双重成像可以清楚地监测这些载药纳米液滴的分布。在 LIFU 照射下，Fa-Fe@P-PFP-Dox 纳米液滴内的 PFP 经历 ADV，导致 Dox 释放，并促进 Dox 在肿瘤组织中的深层渗透，最终实现了对 NPC 的高效化疗。结果，LIFU 触发的化疗发挥了高效的治疗作用，肿瘤抑制率为 74.24±7.95%。
成功构建了载 Fa 和载药的声纳米液滴，用于 NPC 的双重成像引导的高效化疗。这种新型肿瘤药物输送方法有望为 NPC 患者提供高效、可视化和精确的个性化治疗方法，副作用最小。
