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Homing of ICG-loaded liposome inlaid with tumor cellular membrane to the homologous xenografts glioma eradicates the primary focus and prevents lung metastases through phototherapy†
Biomaterials Science ( IF 6.6 ) Pub Date : 2018-07-11 00:00:00 , DOI: 10.1039/c8bm00604k
He-Lin Xu 1, 2, 3, 4, 5 , Bi-Xin Shen 1, 2, 3, 4, 5 , Meng-Ting Lin 1, 2, 3, 4, 5 , Meng-Qi Tong 1, 2, 3, 4, 5 , Ya-Wen Zheng 1, 2, 3, 4, 5 , Xue Jiang 1, 2, 3, 4, 5 , Wai-Geng Yang 1, 2, 3, 4, 5 , Jian-Dong Yuan 6, 7, 8, 9 , Qing Yao 1, 2, 3, 4, 5 , Ying-Zheng Zhao 1, 2, 3, 4, 5
Affiliation  

Currently, phototherapy initiated by local irradiation with a near-infrared (NIR) laser has emerged as a promising strategy for cancer treatment owing to its low toxicity. However, a key problem for effective phototherapy is how to specifically deliver a sufficient dose of photosensitizers to a tumor focus. Herein, indocyanine green (ICG), a United States Food and Drug Administration (US FDA)-approved photosensitizer, was first encapsulated in an inner aqueous compartment of liposome (ICG-LIP) to improve its stability. Thereafter, tumor cell membranes were isolated from native glioma cells and subsequently inlaid in the bilayer lipid membrane of ICG-LIP to construct cell-like liposomes (ICG-MCLs). ICG was easily encapsulated into the ICG-MCLs with a very high encapsulation efficiency, reaching 78.01 ± 0.72% and its concentration in the final formulation reached 200 μg mL−1. The ICG-MCLs displayed a spherical morphology with a hydrodynamic diameter (Dh) of 115.0 ± 0.5 nm, a PDI of 0.14, and a zeta potential of −11.2 ± 0.9 mV. Moreover, ICG-MCLs exhibited a good stability in terms of particle size and significantly improved the chemical stability of ICG in pH 7.4 PBS at 37 °C. In addition, the temperature of the ICG-MCLs rapidly increased to 63 °C after 10 min irradiation and this was maintained for a longer time. Owing to the cancer cell membrane associated protein, the ICG-MCLs were specifically internalized by homogenous glioma C6 cells in vitro, which resulted in the strong red fluorescence of ICG in cytoplasm. Moreover, in vivo imaging showed that the ICG-MCLs were effectively homed to the tumor site of C6 glioma-bearing Xenograft nude mice through vein injection, which resulted in the temperature of the tumor site rapidly rising, allowing the killing of tumor cells after local NIR irradiation. After treatment with the ICG-MCLs, the primary tumor focus was completely eradicated and lung metastases were effectively inhibited. In conclusion, liposomes inlaid with tumor cellular membranes may serve as an excellent nanoplatform for homologous-targeting phototherapy using ICG.

中文翻译:

将装有肿瘤细胞膜的ICG负载脂质体归巢到同源异种移植神经胶质瘤中,这消除了主要病灶并通过光疗防止了肺转移

目前,由于其低毒性,由近红外(NIR)激光局部照射引发的光疗已成为一种有前途的癌症治疗策略。然而,有效的光疗的关键问题是如何将足够剂量的光敏剂特异性地递送至肿瘤灶。在此,首先将吲哚花青绿(ICG),美国食品和药物管理局(US FDA)批准的光敏剂封装在脂质体(ICG-LIP)的内部水室中,以提高其稳定性。此后,从天然神经胶质瘤细胞中分离出肿瘤细胞膜,随后将其镶嵌在ICG-LIP的双层脂质膜中以构建细胞样脂质体(ICG-MCL)。ICG可以很容易地以非常高的封装效率封装到ICG-MCL中,达到78.01±0。-1。ICG-MCL显示出球形形态,其流体力学直径( D h)为115.0±0.5 nm,PDI为0.14,ζ电位为-11.2±0.9 mV。此外,ICG-MCL在粒径方面表现出良好的稳定性,并显着改善了ICG在37℃的pH 7.4 PBS中的化学稳定性。此外,照射10分钟后,ICG-MCL的温度迅速升高至63°C,并保持了更长的时间。由于癌细胞膜相关蛋白的存在,ICG-MCLs在体外被同质神经胶质瘤C6细胞特异性内化,导致细胞质中ICG发出强烈的红色荧光。而且,体内成像显示,通过静脉注射,ICG-MCLs有效地归巢于C6胶质瘤异种移植裸鼠的肿瘤部位,导致肿瘤部位的温度迅速升高,局部NIR照射后杀死了肿瘤细胞。用ICG-MCL治疗后,原发灶完全消除,肺转移得到有效抑制。总之,镶嵌有肿瘤细胞膜的脂质体可以用作使用ICG进行同源靶向光疗的出色纳米平台。
更新日期:2018-07-11
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