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微流控法制备近红外光热喜树碱/ICG 脂质体及其增强光动力治疗。

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy.

机构信息

Department of Pharmaceutics, School of Pharmacy, Centre for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, People's Republic of China.

Medicinal Function Development of New Food Resources, Jiangsu Provincial Research Center, Zhenjiang, Jiangsu, People's Republic of China.

出版信息

AAPS PharmSciTech. 2023 Mar 22;24(4):82. doi: 10.1208/s12249-023-02539-2.

DOI:10.1208/s12249-023-02539-2
PMID:36949351
Abstract

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro. (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes.

摘要

神经间质细胞发生的恶性肿瘤细胞即神经胶质瘤,其具有进展迅速、预后不良的特点,临床治疗效果仍不理想。我们开发了一种用于快速高效制备牡荆素/吲哚菁绿(ICG)脂质体的微流控芯片(LOC)装置。牡荆素可以从脂质体中释放出来杀死癌细胞,通过协同光动力/光热治疗(PDT/PTT),有可能提高神经胶质瘤的治疗效果并减少治疗时间。通过 LOC 制备了牡荆素/ICG 脂质体,并对其体外理化性质和释放进行了评价。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法和活/死染色用于研究 PDT/PTT 协同作用下牡荆素/ICG 脂质体增强的抗肿瘤作用,同时通过流式细胞术和 Western blot 探讨了相关机制。结果如下:(1)所制备的牡荆素/ICG 脂质体粒径较小,粒径分布均匀,具有显著的低多分散指数(PDI),并且体外累积释放增强。(2)研究发现,该配方脂质体呈现出剂量依赖性的强烈的癌细胞抑制和迁移抑制作用。(3)进一步的机制研究表明,脂质体与近红外辐射结合可显著上调 B 细胞淋巴瘤 2 相关 X(Bax)蛋白水平,并降低 B 细胞淋巴瘤 2(Bcl-2)蛋白水平。基于简单 LOC 平台制备的牡荆素/ICG 脂质体可以有效提高难溶性药物的溶解度,PTT/PDT 的联合作用可以有效提高其抗肿瘤效果,为脂质体的临床转化提供了一种简单有效的方法。

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