Objective: To construct an ideal theranostic nanoplatform (LIP3); to clarify its physicochemical properties; to confirm its characteristics of dual-modality imaging, active-targeting, and cascade amplification therapy for mammary carcinoma; and to perform a preliminary exploration of the cytotoxicity mechanism.
Design: A self-prepared liposome nanosystem, LIP3, can actively target 4T1 cells because the surface is linked with C-RGD. Haematoporphyrin monomethyl ether (HMME), an excellent sonosensitizer entrapped in the lipid bilayer, can function in photoacoustic imaging. Low-intensity focused ultrasound (LIFU) of ultrasound-targeted microbubble destruction (UTMD) promotes localized drug delivery into tumours because PFH, a phase-change substance, is loaded in the LIP3 core, achieving visualization of targeted drug release, and sonodynamic therapy (SDT) can kill tumour cells. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging and precise treatment.
Results: The self-prepared lipid nanosystem, LIP3, meets the above expectations and has ideal physicochemical properties, with a regular sphere with uniform distribution. Contrast-enhanced ultrasound (CEUS), photoacoustic imaging, and bimodal imaging were effective in vitro. In 4T1 cell experiments, the cell capacity was as high as 42.9%, and the cytotoxicity to 4T1 was more than 5 times that of LIP1 (containing AQ4N only) and more than 2 times that of LIP2 (containing only HMME), achieving comparable results as cascade therapy for mammary cancer.
Conclusion: LIP3, a theranostic nanoplatform, was successfully constructed and conformed to the physicochemical characterization of ideal nanoparticles, with active-targeting, dual-modality imaging, visualized drug release, and precise treatment under the action of LIFU. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging, and precise cascade treatment. This unique theranostic NPS with multiple capabilities is expected to be a favourable anti-cancer method in the future.

Keywords: LIFU, SDT, HMME, AQ4N


中文翻译：

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巧妙设计的新型脂质纳米系统：针对体外乳腺癌的靶向保留、受控视觉药物释放和级联放大治疗。

目的：构建理想的治疗诊断纳米平台（LIP3）；阐明其理化性质；确认其双模成像、主动靶向、级联放大治疗乳腺癌的特点；并对细胞毒作用机制进行初步探索。
设计：自行制备的脂质体纳米系统 LIP3 可以主动靶向 4T1 细胞，因为其表面与 C-RGD 相连。血卟啉单甲醚 (HMME) 是一种包裹在脂质双层中的优秀声敏剂，可在光声成像中发挥作用。超声靶向微泡破坏（UTMD）的低强度聚焦超声（LIFU）促进局部药物递送到肿瘤，因为PFH是一种相变物质，装载在LIP3核心中，实现靶向药物释放的可视化和声动力学治疗。 SDT) 可以杀死肿瘤细胞。SDT 为 AQ4N 提供了有利的环境，导致 LIP3 治疗的放大。因此，LIP3呈现靶向聚集和靶向释放，集双模成像和精准治疗于一体。
结果：自行制备的脂质纳米系统LIP3符合上述预期，具有理想的理化性质，呈规则的球形，分布均匀。对比增强超声 (CEUS)、光声成像和双峰成像在体外是有效的。在4T1细胞实验中，细胞容量高达42.9%，对4T1的细胞毒性是LIP1（仅含AQ4N）的5倍以上，是LIP2（仅含HMME）的2倍以上，达到了可比的结果作为乳腺癌的级联疗法。
结论：LIP3是一种治疗诊断纳米平台，在LIFU的作用下成功构建并符合理想纳米粒子的物理化学表征，具有主动靶向、双模态成像、可视化药物释放和精准治疗等特点。SDT 为 AQ4N 提供了有利的环境，导致 LIP3 治疗的放大。因此，LIP3具有靶向聚集和靶向释放的特点，集双模成像、精准级联治疗于一体。这种具有多种功能的独特治疗诊断 NPS 有望成为未来一种有利的抗癌方法。

关键词： LIFU、SDT、HMME、AQ4N