Abstract

Purpose

This study was conducted to prepare a novel tumor-biotargeting high-intensity focused ultrasound (HIFU) synergist for indirectly delivering lipid nanoparticles based on the targeting ability of Bifidobacterium longum to the hypoxic region of solid tumors. The effects of two different delivery methods on the imaging and treatment of solid tumors enhanced by lipid nanoparticles were compared.

Methods

Biotinylated lipid nanoparticles coated with PFH were prepared, cross-linked with B. longum in vitro using a streptavidin-conjugated B. longum antibody (SBA), and observed and detected by laser confocal microscopy and flow cytometry. Solid tumors were treated with HIFU and PFH/BL-NPs. The effects of different delivery methods on the tumor targeting and efficiency of retention of PFH/BL-NPs were observed using Small animal live imaging and frozen sections from small animals.

Results

The PFH/BL-NPs prepared in this study showed good biocompatibility and safety. PFH/BL-NPs and B. longum were cross-linked in a cluster-like manner (confocal laser scanning microscope) in vitro, with a cross-linking rate of 84 ± 6.23% (flow cytometry). The delivery of B. longum followed by that of PFH/BL-NPs not only enhanced the ability of PFH/BL-NPs to target solid tumors (small animal live imaging), but also increased the retention time of PFH/BL-NPs in the tumor (frozen slices), enhancing the effect of the HIFU synergist.

Conclusion

Delivery of B. longum followed by that of PFH/BL-NPs can enhance the imaging of solid tumors and effectively improve the efficiency of HIFU treatment of solid tumors, providing a basis for further clinical work.

中文翻译：

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双歧杆菌介导的高强度聚焦超声用于实体瘤治疗：两种纳米颗粒递送方法的比较。

摘要

目的

进行这项研究以制备一种新型的肿瘤生物靶向高强度聚焦超声（HIFU）增效剂，用于基于长双歧杆菌对实体瘤的低氧区域的靶向能力间接递送脂质纳米颗粒。比较了两种不同的递送方法对脂质纳米颗粒增强的实体瘤的成像和治疗的影响。

方法

制备涂有PFH的生物素化脂质纳米颗粒，使用链霉亲和素偶联的长双歧杆菌抗体（SBA）在体外与长双歧杆菌交联，并通过激光共聚焦显微镜和流式细胞术进行观察和检测。实体瘤用HIFU和PFH / BL-NP治疗。使用小动物活体成像和小动物的冷冻切片观察到不同的递送方法对肿瘤靶向和PFH / BL-NPs保留效率的影响。

结果

这项研究中制备的PFH / BL-NPs具有良好的生物相容性和安全性。PFH / BL-NPs和长双歧杆菌在体外以簇状方式（共聚焦激光扫描显微镜）交联，交联率为84±6.23％（流式细胞仪）。长双歧杆菌的继之以PFH / BL-NPs的递送不仅增强了PFH / BL-NPs靶向实体瘤的能力（小动物活体成像），而且还增加了PFH / BL-NPs在体内的保留时间。肿瘤（冷冻切片），增强HIFU增效剂的作用。

结论

长双歧杆菌的继之以PFH / BL-NPs的交付可以增强实体瘤的成像，并有效提高HIFU治疗实体瘤的效率，为进一步的临床工作提供基础。