In the present study, Death receptor-5 (DR5) antibody conjugated solid lipid nanoparticles (DR5-DAPT-SLNs) has been formulated for effective intracellular of γ-secretase inhibitor, N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) to cancer cells. Emulsification-solvent evaporation, followed by EDC cross-linking methods, was employed to prepare DR5 targeted DAPT-SLNs (DR5-DAPT-SLNs). The formulation was characterized by its particle size, shape, and surface charge. The in vitro & in vivo anticancer efficacy was studied in MDA-MB231 triple negative breast cancer (TNBC) cells and DMBA induced breast cancer model in mice, respectively. The results show that thatDR5-DAPT-SLNs is found to be a spherical shape with an average particle size of 187 ± 0.98 nm and having an average surface charge of 23 ± 2.3 mV. DR5-DAPT-SLNs have higher cytotoxicity in MDA-MB231 cells compared to DAPT-SLNs (non-targeted) and the bulk drug. However, in DR5 negative HEK 293 noncancer cells, the formulation shows minimal cytotoxic effects. The above results, therefore, demonstrate DR5 mediated uptake is responsible for improved cytotoxicity of DAPT. In the in vivo anticancer study, DR5-DAPT-SLNs show greater tumor regression when compared to DAPT-SLNs and the bulk drug. In conclusion, the results of the present study demonstrate that the DR5-DAPT-SLNs selectively target cancer cells and potentiate the anticancer efficacy of DAPT against TNBC cells.

在本研究中，死亡受体-5 (DR5) 抗体偶联固体脂质纳米粒子 (DR5-DAPT-SLNs) 已配制用于有效的细胞内 γ-分泌酶抑制剂 N-[N-(3,5-二氟苯乙酰基) -l -丙氨酰]-S-苯基甘氨酸叔丁酯 (DAPT) 对癌细胞。乳化溶剂蒸发，然后是 EDC 交联方法，用于制备 DR5 靶向 DAPT-SLNs (DR5-DAPT-SLNs)。该制剂的特征在于其粒度、形状和表面电荷。在体外和体内分别在 MDA-MB231 三阴性乳腺癌 (TNBC) 细胞和 DMBA 诱导的小鼠乳腺癌模型中研究了抗癌功效。结果表明，发现DR5-DAPT-SLNs为球形，平均粒径为187±0.98nm，平均表面电荷为23±2.3mV。与 DAPT-SLN（非靶向）和原料药相比，DR5-DAPT-SLN 在 MDA-MB231 细胞中具有更高的细胞毒性。然而，在 DR5 阴性 HEK 293 非癌细胞中，该制剂显示出最小的细胞毒性作用。因此，上述结果表明 DR5 介导的摄取是 DAPT 细胞毒性提高的原因。在体内在抗癌研究中，与 DAPT-SLN 和原料药相比，DR5-DAPT-SLN 显示出更大的肿瘤消退。总之，本研究的结果表明 DR5-DAPT-SLNs 选择性地靶向癌细胞并增强 DAPT 对 TNBC 细胞的抗癌功效。