中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (16): 3410-3419.doi: 10.12307/2025.436

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

双模态成像仿生纳米粒对甲状腺髓样癌的声动力治疗

朱炜薇，凡正超，胥  莹，夏纪筑，赵香芝   

  1. 西南医科大学附属医院超声医学科，四川省泸州市   646000
  • 收稿日期:2024-03-22 接受日期:2024-05-10 出版日期:2025-06-08 发布日期:2024-09-03
  • 通讯作者: 赵香芝，副教授，西南医科大学附属医院超声医学科，四川省泸州市 646000
  • 作者简介:朱炜薇，女，1995年生，四川省成都市人，汉族，西南医科大学附属医院在读硕士，执业医师，主要从事分子影像学研究。
  • 基金资助:
    泸州市指导性科技计划项目(22YYJC0037)，项目负责人：夏纪筑；泸州市指导性科技计划项目(2022JYJ108)，项目负责人：赵香芝；

Dual-modality imaging bionic nanoparticles for sonodynamic therapy on medullary thyroid carcinoma

Zhu Weiwei, Fan Zhengchao, Xu Ying, Xia Jizhu, Zhao Xiangzhi   

  1. Department of Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Received:2024-03-22 Accepted:2024-05-10 Online:2025-06-08 Published:2024-09-03
  • Contact: Zhao Xiangzhi, Associate professor, Department of Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • About author:Zhu Weiwei, Master candidate, Practicing physician, Department of Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    Luzhou City Guiding Science and Technology Plan Project, No. 22YYJC0037 (to XJZ) ; Luzhou City Guiding Science and Technology Plan Project, No. 2022JYJ108 (to ZXZ); Doctoral Start-up Fund Project of Affiliated Hospital of Southwest Medical University (to ZXZ)

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摘要：

文题释义：
声动力疗法：超声具有无创性、可控制性和深层组织高穿透的能力，在临床中被广泛应用。超声与声敏剂协同作用产生具有细胞毒性的活性氧，实现病理性凋亡同时不损伤周围组织，精准发挥抗肿瘤治疗作用。
仿生细胞膜纳米粒：由细胞膜涂层包覆的纳米粒能够获得源细胞膜表面复杂的抗原表达特性而受到广泛关注，包括优越的生物相容性、免疫逃逸、延长血液循环、增强同源靶向和肿瘤穿透能力等优势，为癌症药物的输送提供一种高效的靶向纳米技术平台。

背景：声动力疗法作为一种新型抗肿瘤治疗手段具有非侵入性和时空可控性的特点，在甲状腺髓样癌无创性治疗中具有广阔的应用前景。
目的：制备具有双模态成像能力的仿生癌细胞膜涂层脂质纳米粒，检测纳米粒的理化性质、靶向能力、成像效果、细胞毒性和抗迁移能力。
方法：以二棕榈酰磷脂酰胆碱、二棕榈酰磷脂酰甘油、二硬脂酰磷脂酰乙醇胺-聚乙二醇2000、胆固醇、血卟啉单甲醚、全氟己烷为原料，通过薄膜水合-超声振荡法制备脂质纳米粒HP@LNP，其中血卟啉单甲醚装载于脂质纳米结构的疏水层，全氟己烷装载于脂质纳米结构的亲水核心层内；将甲状腺髓样癌细胞膜包覆于脂质纳米粒HP@LNP表面，构建具有主动靶向甲状腺髓样癌细胞能力的仿生脂质纳米粒MHP@LNP。表征纳米粒MHP@LNP的理化性质、靶向能力、免疫逃逸能力、成像效果、细胞毒性和抗迁移能力。
结果与结论：①脂质纳米粒MHP@LNP呈现典型的核壳结构，粒径为131.06 nm，平均电位为-30.59 mV，凝胶电泳结果显示脂质纳米：粒MHP@LNP与癌细胞膜蛋白图谱相符合，荧光共定位结果显示脂质纳米粒MHP@LNP与癌细胞膜的荧光信号显著重合。脂质纳米粒MHP@LNP纳米粒内血卟啉单甲醚的包封率为87.8%，载药率为14.6%。在低强度聚焦超声刺激下，脂质纳米粒MHP@LNP可发生相变产生微泡，在4 min时超声信号强度达到最大值。在激光照射下，脂质纳米粒MHP@LNP的光声信号强度与其质量浓度呈现线性相关。脂质纳米粒MHP@LNP具有同源细胞靶向能力和免疫逃逸能力。未经低强度聚焦超声照射前的脂质纳米粒MHP@LNP具有良好的生物相容性，而经低强度聚焦超声照射后产生具有细胞毒性的活性氧，有效杀伤甲状腺髓样癌细胞，并抑制甲状腺髓样癌细胞的迁移能力。②结果表明，脂质纳米粒MHP@LNP能够在超声和光声双模态成像引导下实现声动力治疗，用于治疗甲状腺髓样癌。

https://orcid.org/0009-0002-1409-2914 (朱炜薇) 

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 脂质纳米粒, 声动力疗法, 低强度聚焦超声, 声敏剂, 活性氧, 癌细胞膜, 同源靶向, 纳米医学, 光声成像, 双模态成像

Abstract:

BACKGROUND: Sonodynamic therapy represents an innovative antitumor treatment modality characterized by its non-invasiveness and precise spatiotemporal controllability. This approach offers broad prospects for the non-invasive treatment of medullary thyroid carcinoma.

OBJECTIVE: To prepare lipid nanoparticles coated with a biomimetic cancer cell membrane capable of dual-modality imaging, and to detect the physicochemical properties, targeting ability, imaging efficacy, cytotoxicity, and anti-migration capabilities of the nanoparticles.

METHODS: Dipalmitoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol, distearoyl phosphatidylethanolamine-PEG2000, cholesterol, hematoporphyrin monomethyl ether, and perflexane were used as raw materials. Nanoparticles HP@LNP were synthesized using a thin-film hydration-ultrasonication technique, encapsulating hematoporphyrin monomethyl ether within the hydrophobic layer and perflexane within the hydrophilic core of lipid nanostructures. Subsequently, the surface of these nanoparticles HP@LNP was coated with medullary thyroid carcinoma cell membrane, resulting in the creation of biomimetic lipid nanoparticles (MHP@LNP) with active targeting capabilities towards medullary thyroid carcinoma cells. The physicochemical properties, targeting ability, immune evasion capacity, imaging effect, cytotoxicity, and anti-migration properties of MHP@LNP nanoparticles were characterized. 
RESULTS AND CONCLUSION: (1) The synthesized MHP@LNP nanoparticles demonstrated a typical core-shell structure, with a diameter of 131.06 nm and an average zeta potential of -30.59 mV. Gel electrophoresis confirmed that the protein profile of the MHP@LNP nanoparticles closely matched that of the cancer cell membrane. Fluorescent colocalization studies indicated a significant overlap between the fluorescence signals of the nanoparticles and the cancer cell membrane. The encapsulation rate and drug loading rate of hematoporphyrin monomethyl ether in MHP@LNP nanoparticles were 87.8% and 14.6% respectively. Upon stimulation with low-intensity focused ultrasound, the MHP@LNP nanoparticles underwent a phase transition, forming microbubbles with ultrasound signal intensity peaking at 4 minutes. Under laser irradiation, the photoacoustic signal intensity was found to be linearly correlated with the mass concentration of the nanoparticles. The MHP@LNP nanoparticles exhibited homologous cell targeting and immune evasion capabilities. Prior to exposure to low-intensity focused ultrasound, the MHP@LNP nanoparticles showed good biocompatibility. However, following ultrasound irradiation, they produced cytotoxic reactive oxygen species, had lethal effect on medullary thyroid carcinoma cells, and inhibited the migration of medullary thyroid carcinoma cells. (2) These findings indicate that MHP@LNP nanoparticles can achieve sonodynamic therapy for the treatment of thyroid medullary carcinoma under ultrasound and photoacoustic dual-modality imaging guidance.

Key words: lipid nanoparticle, sonodynamic therapy, low-intensity focused ultrasound, sonosensitizer, reactive oxygen species, cancer cell membrane, homologous targeting, nanomedicine, photoacoustic imaging, dual-modality imaging

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