In this paper, we describe the preparation of polymeric nanoparticles (NPs) loaded with sorafenib for the treatment of hepatocellular carcinoma (HCC). A synthetic brush copolymer, named PHEA-BIB-ButMA (PBB), was synthesized by Atom Trasnfer Radical Polymerization (ATRP) starting from the α-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) and poly butyl methacrylate (ButMA). Empty and sorafenib loaded PBB NPs were, then, produced by using a dialysis method and showed spherical morphology, colloidal size, negative ζ potential and the ability to allow a sustained sorafenib release in physiological environment.

Sorafenib loaded PBB NPs were tested in vitro on HCC cells in order to evaluate their cytocompatibility and anticancer efficacy if compared to free drug. Furthermore, the enhanced anticancer effect of sorafenib loaded PBB NPs was demonstrated in vivo by using a xenograft model, by first allowing Hep3B cells to grow subcutaneously into nude mice and then administering sorafenib as free drug or incorporated into NPs via intraperitoneal injection. Finally, in vivo biodistribution studies were performed, showing the ability of the produced drug delivery system to accumulate in a significant manner in the solid tumor by passive targeting, thanks to the enhanced permeability and retention effect.

在本文中，我们描述了载有索拉非尼的聚合物纳米颗粒（NPs）的制备，用于治疗肝细胞癌（HCC）。以α-聚（N -2-羟乙基）-d，1-天冬酰胺（PHEA）和聚丁基为原料，通过原子转移自由基聚合（ATRP）合成了名为PHEA-BIB-ButMA（PBB）的合成刷状共聚物。甲基丙烯酸酯（ButMA）。然后，通过透析方法制得了空的，装有索拉非尼的PBB NP，并显示了球形形态，胶体大小，负ζ电位以及允许索拉非尼在生理环境中持续释放的能力。

负载索拉非尼的PBB NPs在HCC细胞上进行了体外测试，以评估其细胞相容性和与游离药物相比的抗癌功效。此外，通过使用异种移植模型在体内证明了索拉非尼负载的PBB NP的增强的抗癌作用，首先使Hep3B细胞皮下生长成裸鼠，然后将索拉非尼作为游离药物给药或通过腹膜内注射掺入NP中。最后，进行了体内生物分布研究，显示了由于增强的通透性和保留作用，所产生的药物传递系统能够通过被动靶向以显着方式在实体瘤中蓄积。