雷洛昔芬 (RLX) 是一种选择性雌激素受体调节剂 (SERM)，其临床效用因严重副作用和不利的药物特性而受到影响。为了解决这些问题，RLX 尝试了转铁蛋白 (Tf) 共轭氧化石墨烯纳米带 (GONR) 平台。通过使用 1, 2-二硬脂酰基-sn-甘油-3 磷酸乙醇胺-聚乙二醇 (DSPE-PEG) 进行表面修饰，可以提高 GONR 在生物介质中的稳定性。使用 EDC-NHS 化学将 Tf 分子共价连接到 DSPE-PEG (DPT)。然后用 DSPE-PEG (DP) 或 DPT 修饰 GONR 的表面，并负载 RLX（GDP-RLX 和 GDPT-RLX）。最终制剂的载药量和稳定性进行了表征。在所有体外和体内研究中评估和比较了纯 RLX、GDP-RLX 和 GDPT-RLX 的抗癌活性。体外细胞系研究表明，GDPT-RLX 具有显着高的细胞毒性、细胞摄取、细胞凋亡诱导、G2/M 期阻滞、抗迁移特性和凋亡蛋白表达，其次是 GDP-RLX 和 RLX。 GDPT-RLX 的药代动力学和肿瘤生物分布也非常出色。体内肿瘤治疗和肿瘤评价结果也与体外数据一致。 Tf 结合的 GDPT-RLX 代表了一种有前景的 RLX 靶向持续递送方法，具有增强的治疗功效。版权所有 © 2024。由 Elsevier B.V. 出版。

The clinical utility of raloxifene (RLX), a selective estrogen receptor modulator (SERM), has been compromised by severe side effects and unfavorable drug properties. To address these, a transferrin (Tf) conjugated graphene oxide nanoribbon (GONR) platform was tried for RLX. The stability of GONRs in biological media was improved by surface modification with 1, 2-Distearoyl-sn-glycero-3 phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG). The Tf molecule was covalently attached to DSPE-PEG (DPT) using EDC-NHS chemistry. The surface of GONR was then modified with DSPE-PEG (DP) or DPT and loaded with RLX (GDP-RLX and GDPT-RLX). The final formulations were characterized for drug loading and stability. The anticancer activities of pure RLX, GDP-RLX, and GDPT-RLX were evaluated and compared in all the in vitro and in vivo studies. In vitro cell line studies showed that GDPT-RLX have significantly high cytotoxicity, cellular uptake, apoptosis induction, G2/M phase arrest, anti-migration properties, and apoptotic protein expression, followed by GDP-RLX and RLX. Pharmacokinetics and tumor biodistribution were also found to be excellent with GDPT-RLX. The in vivo tumor therapy and tumor evaluation outcomes were also consistent with the in vitro data. The Tf conjugated GDPT-RLX represents a promising approach for targeted and sustained delivery of RLX with enhanced therapeutic efficacy.Copyright © 2024. Published by Elsevier B.V.