Mammalian Cell Culture Laboratory, Biological Engineering Program, Faculty of Engineering, King Mongkut's University of Technology Thonburi, Bangkok, Thailand.
Hair Diseases and Hair Transplantation Division, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Int J Nanomedicine. 2020 Nov 6;15:8717-8737. doi: 10.2147/IJN.S267119. eCollection 2020.
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.
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.
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.
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.
药物在内溶酶体中的降解已被广泛认为是生物利用度差的原因之一。为了使分子逃脱破坏性命运，一种策略是在药物载体中引入光敏部分，从而使内体和内溶酶体在照射后能够渗透。本文提出了一种由具有成本效益的大豆磷脂与近红外（NIR）敏化剂 IR-820 混合组成的替代递药纳米系统，用于负载各种活性化合物，并在低细胞毒性作用下触发内溶酶体逃逸。
采用薄膜水化法制备 IR-820 结合磷脂的纳米粒子，以包封不同的分子探针和药物模型。通过动态光散射、透射电子显微镜以及紫外-可见和荧光光谱技术对纳米粒子进行了体外表征。评估了光化学产物的近红外相应生成、含量释放以及对 HaCaT 角质形成细胞系的细胞毒性。使用细胞化学标记物和带有共定位分析的荧光探针监测细胞内吞作用和内溶酶体逃逸。
IR-820 结合的纳米粒子显示出近红外触发的单线态氧存在、纳米粒子结构和释放速率的变化，而没有细胞毒性。此外，该纳米平台似乎增强了大分子的细胞摄取。细胞化学标记物的定位和荧光信号的共定位分析表明，在近红外照射后，载体内溶酶体逃逸。
将 IR-820 纳入大豆磷脂基础成分中为所形成的纳米粒子提供了近红外响应性，特别是载物的内溶酶体逃逸，同时保持了作为药物载体的有益特性。这种替代递药纳米医学系统具有未来的潜力，可利用时间和空间可控的近红外触发以及与近红外生物调节的协同治疗效果，提供细胞溶质药物的高生物利用度。
