Drug-Loaded Acoustic Nanodroplet for Dual-Imaging Guided Highly Efficient Chemotherapy Against Nasopharyngeal Carcinoma.
Drug-Loaded Acoustic Nanodroplet for Dual-Imaging Guided Highly Efficient Chemotherapy Against Nasopharyngeal Carcinoma.
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用于双成像引导高效鼻咽癌化疗的载药声纳米滴
DOI：
10.2147/ijn.s377514
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发表时间：
2022
影响因子：
8
通讯作者：
中科院分区：
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背景化疗是治疗鼻咽癌的重要手段。但由于缺乏选择性、肿瘤蓄积不足、肿瘤分布不均匀以及严重的全身毒性，导致这些药物的疗效不理想。虽然更精确的药物递送、按需药物释放和药物的深度扩散（药物在肿瘤中的均匀分布）可以改善应用，但它们仍然具有挑战性。具有双重成像能力的化学药物声学纳米液滴有望解决这些问题。方法采用复乳法将叶酸修饰的聚乳酸-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Fe 3 O 4纳米粒（命名为Fa-Fe@P-PFP-Dox）组装在一起。合成完成后，研究了LIFU触发的声学液滴蒸发（ADV）效应、LIFU触发的药物释放、细胞靶向能力、体外细胞杀伤效应、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。结果PA/MR双重成像可清晰监测载药纳米液滴的分布。在LIFU照射后，Fa-Fe@P-PFP-Dox纳米液滴内的PFP经历ADV，这导致Dox的释放并促进Dox在肿瘤组织中的深度渗透，最终实现针对NPC的高效化疗。结果表明，LIFU触发的化疗发挥了高效的治疗效果，肿瘤抑制率为74.24 ± 7.95%。结论成功构建了FA修饰的载药声学纳米液滴，可用于双成像引导的鼻咽癌高效化疗。这种新型的肿瘤给药方法有望为NPC患者提供一种高效、可视化、精确的个性化治疗方法，且副作用最小。
Background 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. Methods Folate (Fa)-modified and doxorubicin (Dox)-loaded acoustic poly (lactic‐co‐glycolic acid) (PLGA), low intensity focused ultrasound (LIFU)-responsive perfluoropentane (PFP) and Fe3O4 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. Results 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%. Conclusion 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.