Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 9190501Jerusalem, Israel.
Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, 08193 Bellaterra, Barcelona, Spain.
ACS Nano. 2023 Feb 14;17(3):1946-1958. doi: 10.1021/acsnano.2c05733. Epub 2022 Dec 5.
With the aim to locally enhance the efficacy of cancer nanotherapies, here we present metal iron based magnetoplasmonic drug-loaded nanocapsules (MAPSULES), merging powerful external magnetic concentration in the tumor and efficient photothermal actuation to locally boost the drug therapeutic action at ultralow drug concentrations. The MAPSULES are composed of paclitaxel-loaded polylactic--glycolic acid (PLGA) nanoparticles partially coated by a nanodome shape iron/silica semishell. The iron semishell has been designed to present a ferromagnetic vortex for incorporating a large quantity of ferromagnetic material while maintaining high colloidal stability. The large iron semishell provides very strong magnetic manipulation via magnetophoretic forces, enabling over 10-fold higher trapping efficiency in microfluidic channels than typical superparamagnetic iron oxide nanoparticles. Moreover, the iron semishell exhibits highly damped plasmonic behavior, yielding intense broadband absorbance in the near-infrared biological windows and photothermal efficiency similar to the best plasmonic nanoheaters. The therapeutic assays in a mouse xenograft tumor model show a high amplification of the therapeutic effects by combining magnetic concentration and photothermal actuation in the tumor, leading to a complete eradication of the tumors at ultralow nanoparticle and drug concentration (equivalent to only 1 mg/kg PLGA nanoparticles containing 8 μg/kg of paclitaxel, i.e., 100-500-fold lower than the therapeutic window of the free and PLGA encapsulated drug and 13-3000-fold lower than current nanotherapies combining paclitaxel and light actuation). These results highlight the strength of this externally controlled and amplified therapeutic approach, which could be applied to locally boost a wide variety of drugs for different diseases.
为了局部提高癌症纳米治疗的疗效，我们在此提出了基于金属铁的磁等离子体载药纳米胶囊（MAPSULES），将强大的外部磁场在肿瘤中的集中作用与高效的光热驱动相结合，以超低药物浓度局部增强药物治疗作用。MAPSULES 由载紫杉醇的聚乳酸-乙醇酸（PLGA）纳米粒部分包覆纳米穹顶形状的铁/二氧化硅半壳组成。铁半壳设计成具有铁磁性涡旋，可容纳大量铁磁性材料，同时保持高胶体稳定性。大的铁半壳通过磁泳力提供非常强的磁操纵，使得在微流道中的捕获效率比典型的超顺磁性氧化铁纳米粒高 10 倍以上。此外，铁半壳表现出高度阻尼的等离子体行为，在近红外生物窗口中产生强烈的宽带吸收，并且光热效率与最佳等离子体纳米加热器相当。在小鼠异种移植肿瘤模型中的治疗试验表明，通过在肿瘤中结合磁集中和光热驱动，可大大增强治疗效果，从而以超低的纳米颗粒和药物浓度（相当于仅 1mg/kg 的 PLGA 纳米颗粒中含有 8μg/kg 的紫杉醇，即比游离紫杉醇和 PLGA 包封药物的治疗窗低 100-500 倍，比结合紫杉醇和光驱动的当前纳米疗法低 13-3000 倍）完全消除肿瘤。这些结果突出了这种外部控制和放大治疗方法的优势，可应用于局部增强多种不同疾病的各种药物的疗效。
