仿生纳米递药平台：血小板膜包覆染料木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.

机构信息

School of Pharmacy, Hangzhou Medical College, Hangzhou, 310013, People's Republic of China.

Department of Traditional Chinese Medicine, Zhejiang Pharmaceutical University, Ningbo, 315500, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Oct 16;19:10455-10478. doi: 10.2147/IJN.S479438. eCollection 2024.

DOI:10.2147/IJN.S479438

PMID:39430311

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11491070/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Biomimetic nanomedicine provides a new strategy for the precision treatment of lung cancer in clinical practice.

摘要

背景

染料木黄酮（Gen）是一种天然多酚化合物，已成为治疗肺癌的有前途的候选药物。然而，由于其溶解度低、生物利用度低和毒性副作用，Gen 的临床应用受到限制。为了解决这些挑战，构建了一种仿生递药平台，该平台使用源自天然细胞的细胞膜作为载体材料。这种创新方法旨在促进靶向药物递送，并解决合成材料生物相容性的问题。

方法

首先，采用乙醇注入法制备载有 Gen 的脂质体（LPs@Gen）。然后，通过混合血小板膜（PLTM）和 LPs@Gen 后共挤出，获得 PLTM-LPs@Gen。此外，还研究了 PLTM-LPs@Gen 的生物学和物理化学性质。最后，通过细胞模型和荷瘤裸鼠模型评估了 PLTM-LPs@Gen 对肺癌的靶向能力、治疗效果和安全性。

结果

LPs@Gen 的最佳制备比例为 Gen：大豆卵磷脂：胆固醇：DSPE-PEG2000（3:30:5:10，质量比），而 LPs@Gen 和 PLTM 的理想融合比例为 1:1。PLTM-LPs@Gen 的粒径为 108.33±1.06nm，包封率和载药量分别为 94.29%和 3.09%。Gen 从 PLTM-LPs@Gen 中持续缓慢释放。此外，PLTM-LPs@Gen 在一周内具有良好的稳定性。体外细胞摄取和体内分布实验结果表明，载体材料 PLTM-LPs 具有免疫逃逸能力和肿瘤靶向能力。因此，它在体外和体内肿瘤模型中表现出比游离药物和传统 LPs 更好的治疗效果。此外，安全性实验表明 PLTM-LPs@Gen 具有良好的生物相容性。