生物启发的纳米传递平台：针对靶向肺癌治疗
Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy
影响因子:6.50000
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
摘要
天然多酚化合物Genastein（Gen）已成为肺癌治疗的有前途的候选者。但是，由于其溶解性差，生物利用度低和有毒副作用，因此Gen的潜在临床应用受到限制。为了应对这些挑战，构建了带有天然细胞的细胞膜的仿生递送平台，作为载体材料。这种创新的方法旨在促进靶向药物输送并解决合成材料的生物相容性问题。首先，使用乙醇注入方法制备了装有Gen（LPS@gen）的脂质体（LPS）。随后，在混合血小板膜（PLTM）和LPS@gen之后，通过共截断获得了PLTM-LPS@gen。此外，研究了PLTM-LPS@gen的生物学和物理化学特性。最后，使用细胞模型和含有肿瘤的裸鼠模型评估了PLTM-LPS@Gen的靶向能力，治疗功效和安全性。 1：1。 PLTM-LPS@Gen的粒径为108.33±1.06 nm，封装效率和药物负荷分别为94.29％和3.09％。 Gen从PLTM-LPS@Gen连续释放。此外，PLTM-LPS@Gen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的结果表明，载体材料PLTM-LP具有免疫逃生能力和肿瘤靶向能力。因此，它表现出比免费药物和体内肿瘤模型的免费药物和传统LPS更好的治疗作用。此外，安全实验表明，PLTM-LPS@gen具有良好的生物相容性。生物映射纳米医学在临床实践中为肺癌的精确治疗提供了一种新的策略。
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.