Purpose: The degradation of drugs within endolysosomes has been widely addressed as a cause of poor bioavailability. One of the strategies to allow molecules to escape from a destructive fate is to introduce a photosensitizing moiety into a drug carrier enabling the permeabilization of endosomes and endolysosomes upon irradiation. This paper presents an alternative delivery nanosystem composed of cost-effective soybean phosphatides mixed with IR-820, a near-infrared (NIR) sensitizer, to load various active compounds and trigger an endolysosomal escape with a low cytotoxic effect.
Methods: IR-820-incorporated phosphatides-based nanoparticles were formulated using a thin-film hydration method to encapsulate different molecular probes and a drug model. The nanoparticles were characterized in vitro using dynamic light scattering, transmission electron microscopy, as well as ultraviolet–visible and fluorescence spectroscopy techniques. The NIR-corresponding generation of the photochemical products, the content release, and the cytotoxicity toward the HaCaT keratinocyte cell line were evaluated. The cellular internalization and endolysosomal escape were monitored using a cytochemical marker and fluorescent probes with a colocalization analysis.
Results: The IR-820-combined nanoparticles revealed the NIR-triggered changes in the singlet oxygen presence, nanoparticle architecture, and release rate without being cytotoxic. Additionally, the nanoplatform appeared to enhance cellular uptake of the macromolecules. The localization of the cytochemical marker and the colocalization analysis on the fluorescence signals of the encapsulated fluorophore and the lysosome-labeling reporter implied the transient endolysosomal escape of the cargo within the HaCaT cells after NIR irradiation.
Conclusion: The inclusion of IR-820 into a soybean-phosphatides base ingredient provides NIR responsiveness, particularly the endolysosomal escape of the payload, to the formulated nanoparticles, while preserving the beneficial properties as a drug carrier. This alternative delivery nanomedicine system has future potential to provide high bioavailability of cytosolic drugs utilizing time- and spatial-controllable NIR triggerability as well as the synergistic therapeutic effects with NIR-biomodulation.

Keywords: IR-820, soybean phosphatides, NIR-responsive nanoparticles, endolysosomal escape


中文翻译：

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将 IR-820 包含在基于大豆磷脂的纳米颗粒中，用于 HaCaT 角质形成细胞的近红外触发释放和内溶酶体逃逸，细胞毒性水平不显着

目的：内溶酶体内的药物降解已被广泛认为是生物利用度差的原因。使分子摆脱破坏性命运的策略之一是将光敏部分引入药物载体中，从而在照射时使内体和内溶酶体透化。本文提出了一种替代递送纳米系统，该系统由具有成本效益的大豆磷脂与近红外 (NIR) 增敏剂 IR-820 混合而成，可加载各种活性化合物并触发内溶酶体逃逸，且细胞毒性低。
方法：IR-820 结合的磷脂基纳米颗粒使用薄膜水合方法配制，以封装不同的分子探针和药物模型。使用动态光散射、透射电子显微镜以及紫外-可见和荧光光谱技术在体外对纳米颗粒进行表征。评估了光化学产物的 NIR 对应生成、内容物释放和对 HaCaT 角质形成细胞系的细胞毒性。使用细胞化学标记和荧光探针与共定位分析监测细胞内化和内溶酶体逃逸。
结果：IR-820 结合的纳米颗粒揭示了近红外触发的单线态氧存在、纳米颗粒结构和释放速率的变化，而没有细胞毒性。此外，纳米平台似乎增强了大分子的细胞吸收。细胞化学标记的定位以及对封装荧光团和溶酶体标记报告基因的荧光信号的共定位分析暗示了近红外照射后 HaCaT 细胞内货物的瞬时内溶酶体逃逸。
结论：将 IR-820 添加到大豆磷脂基础成分中，可提供 NIR 响应性，特别是有效负载的内溶酶体逃逸，对配制的纳米颗粒，同时保留作为药物载体的有益特性。这种替代递送纳米药物系统具有未来潜力，利用时间和空间可控的 NIR 触发性以及与 NIR 生物调节的协同治疗效果来提供细胞溶质药物的高生物利用度。

关键词： IR-820，大豆磷脂，近红外响应纳米颗粒，内溶酶体逃逸