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脂质包覆介孔硅纳米粒子在癌症治疗中的增效与药物递送。

Enhanced efficacy and drug delivery with lipid coated mesoporous silica nanoparticles in cancer therapy.

机构信息

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany; Department of Pharmacy, The University of Lahore, Lahore, Pakistan.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany; Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan.

出版信息

Eur J Pharm Biopharm. 2021 Aug;165:31-40. doi: 10.1016/j.ejpb.2021.04.020. Epub 2021 May 4.

Abstract

The exposure of cancer cells to subtherapeutic drug concentrations results in multidrug resistance (MDR). The uniqueness of mesoporous silica nanoparticles (MSNPs) with larger surface area for higher drug loading can solve the issue by delivering higher amounts of chemotherapeutics to the cancer cells. However, premature drug release and lower biocompatibility remain challenging. Lipid coating of MSNPs at the same time, can enhance the stability and biocompatibility of nanocarriers. Furthermore, the lipid coating can reduce the systemic drug release and deliver higher amounts to the tumor site. Herein, lipid coated MSNPs were prepared by utilizing cationic liposomes and further investigations were made. Our studies have shown the higher entrapment of doxorubicin (Dox) to MSNPs due to availability of porous structure. Lipid coating could provide a barrier to sustain the release of drug along with reduced premature leakage. In addition, the biocompatibility and enhanced interaction of cationic liposomes to cell membranes resulted in better cellular uptake. Lipid coated silica nanoparticles have shown higher cellular toxicity as compared to non-lipid coated particles. The increase in cytotoxicity with time supports the hypothesis of sustained release of drug from lipid coated MSNPs. We propose the Lip-Dox-MSNPs as an effective approach to treat cancer by delivering and maintaining effective concentration of drugs to the tumor site without systemic side effects.

摘要

癌细胞暴露于亚治疗药物浓度会导致多药耐药(MDR)。介孔硅纳米粒子(MSNPs)具有更大的表面积,可用于更高的药物负载量,通过向癌细胞输送更多的化疗药物可以解决这个问题。然而,药物过早释放和较低的生物相容性仍然是挑战。同时对 MSNPs 进行脂质涂层,可以提高纳米载体的稳定性和生物相容性。此外,脂质涂层可以减少系统药物释放并将更多药物递送到肿瘤部位。本文通过利用阳离子脂质体来制备脂质涂层的 MSNPs,并进一步进行了研究。我们的研究表明,由于多孔结构的存在,阿霉素(Dox)更容易被 MSNPs 包封。脂质涂层可以提供一个屏障,以维持药物的释放,同时减少药物的过早泄漏。此外,阳离子脂质体与细胞膜的生物相容性和增强的相互作用导致更好的细胞摄取。与非脂质涂层颗粒相比,脂质涂层的硅纳米颗粒显示出更高的细胞毒性。随着时间的推移,细胞毒性的增加支持了从脂质涂层 MSNPs 中持续释放药物的假设。我们提出 Lip-Dox-MSNPs 作为一种有效的治疗癌症的方法,通过将药物输送到肿瘤部位并维持有效的药物浓度,而不会产生全身副作用。

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