制备负载来曲唑 (LTZ) 的树枝状纳米脂质体，用于靶向递送至乳腺癌细胞。尝试使用阳离子肽树枝状聚合物 (PD) 和癌症特异性配体转铁蛋白 (Tf) 进行表面修饰。使用固相肽合成法合成精氨酸封端的 PD (D-1) 和精氨酸封端的脂化 PD (D-2)，通过制备型 HPLC 进行纯化，并使用 1 HNMR、MS 和 DSC 分析进行表征。用 Tf 和/或 PD 对载药脂质体进行表面修饰。使用 FTIR、DSC、1HNMR、XRD 和 TEM 对配方进行表征。与 Tf 结合的 LTZ 脂质体 (LTf) 和 Tf/D-2 结合的 LTZ 脂质体 (LTfD-2) 显示出更大的细胞毒性潜力（IC50 分别 = 95.03 µg/mL 和 23.75 µg/mL），并且与 MCF7 细胞相比，MCF7 细胞中的细胞摄取增强。普通LTZ。 Tf（Tf 受体介导的内化）的阻断研究揭示了 LTf 和 LTfD-2 的摄取减少，证实了 Tf 在 Tf 结合脂质体的摄取中的作用。与普通 LTZ (605 mm3) 和未结合的 LTZ 脂质体 (LP) (300 mm3) 相比，LTfD-2 静脉注射治疗使雌性 BALB/c-裸鼠 (145 mm3) 的肿瘤体积减少最多。体内生物分布研究表明，LTfD-2 治疗小鼠的肿瘤组织和肝脏中的荧光高于 LTf 或 LP 治疗小鼠。 TUNEL 测定和 ROS 检测测定表明，免疫组织化学研究表明 LTfD-2 具有更大的凋亡潜力。该研究揭示了所开发的 LTZ 脂质体纳米载体的卓越治疗效果，该载体使用 PD 来提高转染效率，此外还通过附加靶向配体以将活性药物靶向乳腺癌细胞来修饰表面特性。版权所有 © 2023。由 Elsevier B.V. 出版。

Letrozole (LTZ) loaded dendrimeric nano-liposomes were prepared for targeted delivery to breast cancer cells. Surface modification with cationic peptide dendrimers (PDs) and a cancer specific ligand, transferrin (Tf), was attempted. Arginine-terminated PD (D-1) and Arginine-terminated, lipidated PD (D-2) were synthesized using Solid Phase Peptide Synthesis, purified by preparative HPLC and characterized using 1HNMR, MS and DSC analyses. Surface modification of drug loaded liposomes with Tf and/or PD was carried out. Formulations were characterized using FTIR, DSC, 1HNMR, XRD and TEM. Tf-conjugated LTZ liposomes (LTf) and Tf/D-2-conjugated LTZ liposomes (LTfD-2) showed greater cytotoxic potential (IC50 = 95.03 µg/mL and 23.75 µg/mL respectively) with enhanced cellular uptake in MCF7 cells compared to plain LTZ. Blocking studies of Tf (Tf-receptor mediated internalization) revealed decreased uptake of LTf and LTfD-2 confirming the role of Tf in uptake of Tf-conjugated liposomes. Intravenous treatment with LTfD-2 caused highest reduction in tumor volumes of female BALB/c-nude mice (145 mm3) compared to plain LTZ (605 mm3) and unconjugated LTZ liposomes (LP) (300 mm3). In vivo biodistribution studies revealed higher fluorescence in tumor tissue and liver of LTfD-2 treated mice than LTf or LP treatment. Immunohistochemical studies revealed greater apoptotic potential of LTfD-2 as indicated by TUNEL assay and ROS detection assay. The study reveals the superior therapeutic efficacy of the developed LTZ liposomal nanocarriers using PDs to enhance the transfection efficiency in addition to modifying the surface characteristics by attaching a targeting ligand for active drug targeting to breast cancer cells.Copyright © 2023. Published by Elsevier B.V.