乳腺癌是一种难以治疗且具有不良临床预后的疾病。紫杉醇（PTX）是一种一线化疗药物，但由于副作用、高剂量、非特异性组织分布和药物耐药性等限制，它存在一定的局限性。一种表观遗传修饰剂沃利诺斯塔（VOR）被认为可以提高PTX的疗效，因此为了解决传统PTX制剂的问题，我们设计了PTX和VOR结合的白蛋白纳米粒子（PTX-VOR-BSA-NPs），采用了反溶剂沉淀技术，其中白蛋白被用作载体和靶向药物。PTX-VOR-BSA-NPs的粒径约为140 nm，多分散指数约为0.18，PTX和VOR的封装率分别约为78%和68%。从PTX-VOR-BSA-NPs中观察到PTX和VOR的双模式释放，首先是2小时的爆发式释放，然后是持续释放，持续到24小时。在MCF-7细胞系中观察到显著较低的细胞存活率，而在MDA-MB-231细胞中发现了有效的细胞摄取。此外，与游离PTX和VOR相比，由于这些药物的协同作用，观察到更高的凋亡指数。在4T1细胞系诱导的乳腺肿瘤模型中，PTX-VOR-BSA-NPs还展示了优越的药代动力学特征和显著的肿瘤体积减小。此外，与控制组相比，纳米粒子显示了类似的毒性生物标志物水平。总体而言，开发的PTX-VOR-BSA-NPs与市场上的制剂相比，毒性更小而且更有效，确保了产品的强效性和安全性。 © 2023. Controlled Release Society.

Breast cancer is challenging to treat accompanied with poor clinical outcomes. Paclitaxel (PTX) is a first-line chemotherapeutic agent, but possesses limitations due to side effects, high dose, non-specific tissue distribution, and drug resistance. An epigenetic modulator, vorinostat (VOR) is known to enhance PTX efficacy and therefore to resolve the issues of conventional PTX formulations, we designed PTX- and VOR-bound albumin nanoparticles (PTX-VOR-BSA-NPs) using antisolvent precipitation technique where albumin is used as a carrier and a targeting agent. The PTX-VOR-BSA-NPs were of 140 nm size, polydispersity index around 0.18, and about 78% and 68% of entrapment efficiency for PTX and VOR, respectively. A bi-pattern release of both PTX and VOR was observed from PTX-VOR-BSA-NPs with a burst release for 2 h succeeded by sustained release until 24 h. A significantly lower %cell viability was observed in MCF-7 cell lines, while efficient cellular drug uptake was found in MDA-MB-231 cells. Furthermore, a greater apoptotic index was found compared to free PTX and VOR because of the synergistic activity of these drugs. The PTX-VOR-BSA-NPs also showcased superior pharmacokinetic profile and noteworthy reduction in the tumor volume compared to Intaxel in 4T1 cell line-induced breast tumor model. Further, the NPs showed similar levels of toxicity biomarkers as that of control. Overall, the developed PTX-VOR-BSA-NPs were found to have less toxicity and more effectiveness compared to the marketed formulation, thus affirming the generation of a potent as well as and safe product.© 2023. Controlled Release Society.