GLUT1转运蛋白介导的纳米固体脂质载药体系，用于靶向卵巢癌治疗。
GLUT1 transporter-facilitated solid lipid nanoparticles loaded with anti-cancer therapeutics for ovarian cancer targeting.
发表日期：2023 Mar 27
作者：
Saili Jagdale, Mahavir Narwade, Afsana Sheikh, Shadab Md, Rajesh Salve, Virendra Gajbhiye, Prashant Kesharwani, Kavita R Gajbhiye
来源：
INTERNATIONAL JOURNAL OF PHARMACEUTICS
摘要：
用于癌症治疗的治疗法面临的主要难题是将抗癌药物定位到肿瘤部位以及不定向的副作用。卵巢癌的标准疗法仍然存在许多缺陷，因为药物不合理使用会影响健康细胞。纳米医学是一种有吸引力的方法，可以改善抗癌药物的治疗效果。由于制造成本低、生物相容性增强和表面性质可改变，脂质基纳米载体，特别是固体脂质纳米粒子（SLN），在癌症治疗中具有显著的药物输送特性。鉴于其特殊优势，我们开发了负载抗肿瘤（紫杉醇）药物的SLN（PTX-SLN），并用N-乙酰-D-葡萄糖胺（GLcNAc）功能化（GLcNAc-PTX-SLN），以减少GLUT1转运体过度表达的卵巢癌细胞的增殖、生长和转移率。这些粒子具有可观的大小和分布，并表现出良好的血液相容性。使用GLcNAc修饰的SLN，激光共聚焦显微镜、MTT实验和流式细胞术研究表明，细胞摄取率更高，并具有显著的细胞毒性作用。此外，分子对接结果表明GLcNAc与GLUT1之间存在良好的结合亲和力，从而支持该治疗方法在靶向癌症治疗中的可行性。按照SLN的靶向药物传递的组合，我们的结果显示，我们的SLN可以有效治疗卵巢癌。版权所有©2023 Elsevier B.V. 发表。
The therapeutics available for cancer treatment have the major hurdle of site-specific delivery of anti-cancer drugs to the tumor site and non-target specific side effects. The standard therapy for ovarian cancer still poses numerous pitfalls due to the irrational use of drugs affecting healthy cells. As an appealing approach, nanomedicine could revamp the therapeutic profile of anti-cancer agents. Owing to the low manufacturing cost, increased biocompatibility, and modifiable surface properties, lipid-based nanocarriers, particularly solid lipid nanoparticles (SLN), have remarkable drug delivery properties in cancer treatment. Given the extra-ordinary benefits, we developed anti-neoplastic (paclitaxel) drug-loaded SLN (PTX-SLN) and functionalized with N-acetyl-d-glucosamine (GLcNAc) (GLcNAc-PTX-SLN) to reduce the rate of proliferation, growth, and metastasis of ovarian cancer cells over-expressing GLUT1 transporters. The particles presented considerable size and distribution while demonstrating haemocompatibility. Using GLcNAc modified form of SLNs, confocal microscopy, MTT assay, and flow cytometry study demonstrated higher cellular uptake and significant cytotoxic effect. Also, molecular docking results established excellent binding affinity between GLcNAc and GLUT1, complimenting the feasibility of the therapeutic approach in targeted cancer therapy. Following the compendium of target-specific drug delivery by SLN, our results demonstrated a significant response for ovarian cancer therapy.Copyright © 2023. Published by Elsevier B.V.