iRGD功能化相变脂质体纳米液滴用于超声成像引导的喉癌化疗与缺氧调控：体外与体内评价
iRGD-Functionalized Phase-Change Liposomal Nanodroplets for Ultrasound Imaging-Guided Chemotherapy and Hypoxia Modulation in Laryngeal Cancer: In vitro and in vivo Evaluation.
文献信息
| PMID | 42974489 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Wenqian Nong |
| 作者单位 | Basic Medical Sciences Center, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China. |
| 期刊 | International journal of nanomedicine |
| SCI 分区 | Q1 |
| IF | 8.8 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 咽喉科 |
中文摘要
目的： 为解决喉癌化疗疗效的局限性，包括肿瘤选择性蓄积不足、纳米载体药物释放不可控以及化疗耐药相关的缺氧肿瘤微环境，我们开发了一种iRGD功能化相变脂质体纳米液滴iRGD-lipo@CAT-DOX-PFP，用于超声成像引导的化疗与缺氧调控。
方法： 构建iRGD-lipo@CAT-DOX-PFP作为iRGD修饰的脂质体纳米平台，共包载多柔比星（DOX）、过氧化氢酶（CAT）和全氟戊烷（PFP）。在该系统中，iRGD用于增强肿瘤靶向和细胞摄取，PFP作为超声响应性相变核心用于增强对比和触发药物释放，CAT被引入以分解内源性H2O2并改善局部氧可利用性。通过一系列体外和体内实验评价该纳米液滴的理化性质、相变行为、超声成像性能、药物释放特征、细胞摄取、细胞毒性、缺氧调控和抗肿瘤疗效。
结果： iRGD-lipo@CAT-DOX-PFP的平均流体动力学直径为236.10 ± 9.28 nm，具有良好的胶体稳定性，并在TU686喉癌细胞中实现高效细胞内化。在低强度聚焦超声（LIFU）照射下，纳米液滴发生声致液滴汽化，导致超声对比增强和DOX释放加速。体外实验中，iRGD-lipo@CAT-DOX-PFP联合LIFU的细胞毒性大于非相变iRGD-lipo@CAT-DOX制剂，IC50值分别为3.27和11.27 μg/mL。体内实验中，iRGD-lipo@CAT-DOX-PFP + LIFU组的哌莫硝唑信号显著低于游离DOX、lipo@CAT-DOX-PFP + LIFU和iRGD-lipo@DOX-PFP + LIFU组（p < 0.01），并伴有HIF-1α表达降低。完整制剂联合LIFU在受试各组中也产生最强的肿瘤生长抑制（p < 0.001）。
结论： 该多功能脂质体纳米系统在单一平台上整合了肿瘤靶向化疗、缺氧调控、LIFU触发药物释放和超声成像能力。通过实现空间可控的药物释放并联合超声成像引导，iRGD-lipo@CAT-DOX-PFP为喉癌的局部治疗提供了一种有前景的策略。
英文摘要
PURPOSE: To address the limitations in the effectiveness of chemotherapy for laryngeal cancer, including insufficient tumor-selective accumulation, uncontrolled drug release from nanocarriers, and the chemoresistance-associated hypoxic tumor microenvironment, we developed an iRGD-functionalized phase-change liposomal nanodroplet, iRGD-lipo@CAT-DOX-PFP, for ultrasound imaging-guided chemotherapy and hypoxia modulation.
METHODS: iRGD-lipo@CAT-DOX-PFP was constructed as an iRGD-modified liposomal nanoplatform co-encapsulating doxorubicin (DOX), catalase (CAT), and perfluoropentane (PFP). In this system, iRGD was used to enhance tumor targeting and cellular uptake, PFP served as an ultrasound-responsive phase-transition core for contrast enhancement and triggered drug release, CAT was incorporated to decompose endogenous H2O2 and improve local oxygen availability. The nanodroplets were evaluated for their physicochemical properties, phase-transition behavior, ultrasound imaging performance, drug release characteristics, cellular uptake, cytotoxicity, hypoxia modulation, and antitumor efficacy through a series of in vitro and in vivo experiments.
RESULTS: iRGD-lipo@CAT-DOX-PFP exhibited a mean hydrodynamic diameter of 236.10 ± 9.28 nm, good colloidal stability, and efficient cellular internalization in TU686 laryngeal cancer cells. Under low-intensity focused ultrasound (LIFU) irradiation, the nanodroplets underwent acoustic droplet vaporization, resulting in enhanced ultrasound contrast and accelerated DOX release. In vitro, iRGD-lipo@CAT-DOX-PFP combined with LIFU exhibited greater cytotoxicity than the non-phase-change iRGD-lipo@CAT-DOX formulation, with IC50 values of 3.27 and 11.27 μg/mL, respectively. In vivo, the iRGD-lipo@CAT-DOX-PFP + LIFU group showed significantly lower pimonidazole signals than the free DOX, lipo@CAT-DOX-PFP + LIFU, and iRGD-lipo@DOX-PFP + LIFU groups (p < 0.01), accompanied by reduced HIF-1α expression. The complete formulation combined with LIFU also produced the greatest inhibition of tumor growth among the tested groups (p < 0.001).
CONCLUSION: This multifunctional liposomal nanosystem integrates tumor-targeted chemotherapy, hypoxia modulation, LIFU-triggered drug release, and ultrasound imaging capability within a single platform. By enabling spatially controlled drug release together with ultrasound imaging guidance, iRGD-lipo@CAT-DOX-PFP provides a promising strategy for localized treatment of laryngeal cancer.