仿生纳米递送平台：血小板膜包覆的异黄酮纳米系统用于靶向肺癌治疗

Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy

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International Journal of Nanomedicine

影响因子:6.5

分区:医学2区 / 药学2区纳米科技3区

发表日期:2024

作者: Rui Gao, Peihong Lin, Wenjing Yang, Zhengyu Fang, Chunxiao Gao, Bin Cheng, Jie Fang, Wenying Yu

DOI: 10.2147/IJN.S479438

摘要

异黄酮（Genistein, Gen）是一种天然多酚化合物，已成为肺癌治疗的有潜力的候选药物。然而，由于其溶解度差、生物利用度低和毒副作用大，临床应用受到限制。为解决这些问题，构建了一种以天然细胞膜为载体材料的仿生递送平台。这一创新方法旨在促进靶向药物递送，并解决合成材料的生物相容性问题。首先，采用乙醇注射法制备载有异黄酮的脂质体（LPs@Gen）。随后，通过共挤出法，将血小板膜（PLTM）与LPs@Gen混合，获得PLTM-LPs@Gen。此外，研究了PLTM-LPs@Gen的生物学和理化性质。最后，通过细胞模型和裸鼠肿瘤模型评估PLTM-LPs@Gen的靶向能力、治疗效果及安全性。结果显示，LPs@Gen的最佳配比为异黄酮：大豆卵磷脂：胆固醇：DSPE-PEG2000（3:30:5:10，质量比），而LPs@Gen与PLTM的理想融合比为1:1。PLTM-LPs@Gen的粒径为108.33 ± 1.06 nm，包封效率为94.29%，药物负载为3.09%。异黄酮在PLTM-LPs@Gen中持续缓慢释放，且其在一周内表现出良好的稳定性。体外细胞摄取和体内分布实验结果表明，载体材料PLTM-LPs具有免疫逃逸和肿瘤靶向能力。在体内外肿瘤模型中显示出优于游离药物和传统脂质体的治疗效果。此外，安全性试验表明，PLTM-LPs@Gen具有良好的生物相容性。仿生纳米医学为肺癌的精准治疗提供了新的策略。

Abstract

Genistein (Gen), a natural polyphenolic compound, has emerged as a promising candidate for lung cancer treatment. However, the potential clinical application of Gen is limited due to its poor solubility, low bioavailability, and toxic side effects. To address these challenges, a biomimetic delivery platform with cell membranes derived from natural cells as carrier material was constructed. This innovative approach aims to facilitate targeted drug delivery and solve the problem of biocompatibility of synthetic materials.First, the liposomes (LPs) loaded with Gen (LPs@Gen) was prepared using the ethanol injection method. Subsequently, PLTM-LPs@Gen was obtained through co-extrusion after mixing platelet membrane (PLTM) and LPs@Gen. Additionally, the biological and physicochemical properties of PLTM-LPs@Gen were investigated. Finally, the targeting ability, therapeutic efficacy, and safety of PLTM-LPs@Gen for lung cancer were evaluated using both a cell model and a tumor-bearing nude mouse model.The optimal preparation ratio for LPs@Gen was Gen: soybean lecithin: cholesterol: DSPE-PEG2000 (3:30:5:10, mass ratio), while the ideal fusion ratio of LPs@Gen and PLTM was 1:1. The particle size of PLTM-LPs@Gen was 108.33 ± 1.06 nm, and the encapsulation efficiency and drug loading were 94.29% and 3.09% respectively. Gen was released continuously and slowly from PLTM-LPs@Gen. Moreover, PLTM-LPs@Gen exhibited good stability within one week. The results of in vitro cellular uptake and in vivo distribution experiments indicated that the carrier material, PLTM-LPs, has the immune escape ability and tumor targeting ability. Consequently, it showed better therapeutic effects than free drugs and traditional LPs in vitro and in vivo tumor models. In addition, safety experiments demonstrated that PLTM-LPs@Gen possesses good biocompatibility.Biomimetic nanomedicine provides a new strategy for the precision treatment of lung cancer in clinical practice.