Microbubble-based liposomal delivery of dasatinib and COL11A1siRNA for enhanced combination therapy against lung adenocarcinoma

IF 3.674 4区工程技术 Q1 Engineering

Applied Nanoscience Pub Date : 2024-06-10 DOI:10.1007/s13204-024-03057-8

Mahalakshmi Nannan, Sivaramakrishnan Venkatabalasubramanian

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Abstract

Current chemotherapeutic treatments have severely limited effectiveness against tumors. Co-delivery of chemotherapeutic drugs and small interfering RNA (siRNA) in a nanoliposomal drug delivery system is known to selectively improve cytotoxicity against tumors. The current study aimed to achieve augmented combination therapy (Dasatinib-DST and siRNA targeting COL11A1 gene) against lung adenocarcinoma (LUAD) in vitro. The microbubble liposome (MB-LP)-based codelivery system (DST and COL11A1) used in this study was prepared using the thin film hydration method. The resulting codelivery system (MB-LP/DST/siRNA) average size and zeta potential were about 1611.5 nm and − 10.35 mV, respectively. Nevertheless, the average size of the MB-LP drug delivery system alone was 530 nm. The percentage encapsulation efficiency (% EE) of the combination drug (DST and COL11A1^siRNA) in the MB-LP nanodelivery system was 62.9%. The surface morphology of the codelivery system (MB-LP/DST/siRNA) was analysed using a High-Resolution Scanning Electron Microscope (HR-SEM) and a High-Resolution Transmission Electron Microscopy (HR-TEM). Both confirmed the spherical shape of the MB-LP system. MTT-based proliferation analysis in vitro revealed that DST and COL11A1^siRNA containing MB-LP codelivery system caused significant inhibition of cell proliferation against LUAD. This is the first study that suggests the co-delivery of the chemotherapeutic drug (DST) and COL11A1^siRNA using the MB-LP drug delivery system facilitates an anti-proliferative effect against LUAD cells. Additionally, we also conclude that these prospective results strengthen the evidence on the potential of combination therapy (DST and COL11A1^siRNA) against LUAD.

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基于微泡的达沙替尼和 COL11A1siRNA 脂质体递送用于增强肺腺癌的联合治疗

目前的化疗方法对肿瘤的疗效非常有限。众所周知，在纳米脂质体给药系统中联合给药化疗药物和小干扰 RNA（siRNA）可选择性地提高对肿瘤的细胞毒性。本研究旨在体外实现针对肺腺癌（LUAD）的增强型联合疗法（达沙替尼-DST 和靶向 COL11A1 基因的 siRNA）。本研究采用薄膜水合法制备了基于微泡脂质体（MB-LP）的联合给药系统（DST和COL11A1）。所制备的编码递送系统（MB-LP/DST/siRNA）的平均尺寸和 zeta 电位分别约为 1611.5 nm 和 - 10.35 mV。然而，MB-LP 单独给药系统的平均尺寸为 530 nm。混合药物（DST 和 COL11A1siRNA）在 MB-LP 纳米给药系统中的封装效率（EE%）为 62.9%。使用高分辨率扫描电子显微镜（HR-SEM）和高分辨率透射电子显微镜（HR-TEM）分析了编码递送系统（MB-LP/DST/siRNA）的表面形态。两者均证实 MB-LP 系统呈球形。基于 MTT 的体外增殖分析表明，含有 MB-LP 的 DST 和 COL11A1siRNA 编码递送系统能显著抑制 LUAD 细胞的增殖。这是首次研究表明，使用 MB-LP 药物递送系统联合递送化疗药物（DST）和 COL11A1siRNA 可促进对 LUAD 细胞的抗增殖作用。此外，我们还得出结论，这些前瞻性结果加强了联合疗法（DST 和 COL11A1siRNA）治疗 LUAD 的潜力。

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来源期刊

Applied Nanoscience Materials Science-Materials Science (miscellaneous)

CiteScore

7.10

自引率

0.00%

发文量

430

期刊介绍： Applied Nanoscience is a hybrid journal that publishes original articles about state of the art nanoscience and the application of emerging nanotechnologies to areas fundamental to building technologically advanced and sustainable civilization, including areas as diverse as water science, advanced materials, energy, electronics, environmental science and medicine. The journal accepts original and review articles as well as book reviews for publication. All the manuscripts are single-blind peer-reviewed for scientific quality and acceptance.