治疗双重靶向 Au 脂质体的研制用于有效肿瘤靶向和光热治疗。

BACKGROUND: Photothermal therapy (PTT) is an emerging anti-cancer therapeutic strategy that generates hyperthermia to ablate cancer cells under laser irradiation. Gold (Au) coated liposome (AL) was reported as an effective PTT agent with good biocompatibility and excretory property. However, exposed Au components on liposomes can cause instability in vivo and difficulty in further functionalization. RESULTS: Herein, we developed a theranostic dual-layered nanomaterial by adding liposomal layer to AL (LAL), followed by attaching polyethylene glycol (PEG) and radiolabeling. Functionalization with PEG improves the in vivo stability of LAL, and radioisotope labeling enables in vivo imaging of LAL. Functionalized LAL is stable in physiological conditions, and Cu labeled LAL (Cu-LAL) shows a sufficient blood circulation property and an effective tumor targeting ability of 16.4%ID g from in vivo positron emission tomography (PET) imaging. Also, intravenously injected LAL shows higher tumor targeting, temperature elevation in vivo, and better PTT effect in orthotopic breast cancer mouse model compared to AL. The tumor growth inhibition rate of LAL was 3.9-fold higher than AL. CONCLUSION: Based on these high stability, in vivo imaging ability, and tumor targeting efficiency, LAL could be a promising theranostic PTT agent.

背景：光热疗法（PTT）是一种新兴的抗癌治疗策略，它利用激光照射产生的高热来消融癌细胞。金（Au）包覆的脂质体（AL）被报道为一种具有良好生物相容性和排泄性能的有效 PTT 试剂。然而，脂质体上暴露的 Au 成分会导致体内不稳定，并且进一步功能化困难。

结果：本研究通过在 AL 上添加脂质体层（LAL），然后进行聚乙二醇（PEG）功能化和放射性标记，开发了一种治疗诊断两用双层纳米材料。PEG 的功能化提高了 LAL 的体内稳定性，放射性同位素标记使 LAL 的体内成像成为可能。功能化的 LAL 在生理条件下稳定，Cu 标记的 LAL（Cu-LAL）显示出足够的血液循环特性和 16.4%ID g 的有效肿瘤靶向能力，从体内正电子发射断层扫描（PET）成像中可以看出。此外，与 AL 相比，静脉注射的 LAL 表现出更高的肿瘤靶向性、体内温度升高和更好的 PTT 效果。LAL 的肿瘤生长抑制率比 AL 高 3.9 倍。

结论：基于这种高稳定性、体内成像能力和肿瘤靶向效率，LAL 可能成为一种有前途的治疗诊断 PTT 试剂。