Until recently, there have been limited options for patients with bone metastatic castration-resistant prostate cancer (BmCRPC) following the failure of or development of resistance to docetaxel (DTX), which is one of the frontline treatments. Sterol regulatory element-binding protein 1 (SREBP1) is reported to regulate abnormal lipid metabolism and to promote the progression and metastasis of prostate cancer (PCa). The siRNA interferes SREBP1 may provide an efficient treatment when combined with DTX.

Methods: In this study, lipoic acid (LA) and cross-linked peptide-lipoic acid micelles were cross-linked (LC) for DTX and siSREBP1 delivery (LC/D/siR). Then, cell membrane of PCa cells (Pm) and bone marrow mesenchymal stem cells (Bm) were fused for cloaking LC/D/siR (PB@LC/D/siR). Finally, the synthesized PB@LC/D/siR was evaluated in vitro and in vivo.

Results: PB@LC/D/siR is internalized in PCa cells by a mechanism of lysosome escape. Tumor targeting and bone homing studies are evaluated using bone metastatic CRPC (BmCRPC) models, both in vitro and in vivo. Moreover, the enhanced anti-proliferation, anti-migration and anti-invasion capacities of DTX- and siSREBP1- loaded PB@LC (PB@LC/D/siR) were observed in vitro. Furthermore, PB@LC/D/siR was able to suppress the growth of the tumor effectively with deep tumor penetration, high safety and good protection of the bone at the tumor site. Additionally, the mRNA levels and protein levels of SREBP1 and SCD1 were able to be significantly downregulated by PB@LC/D/siR.

Conclusion: This study presented a bone-cancer dual-targeting biomimetic nanodelivery system for bone metastatic CRPC.

直到最近，多西他赛（DTX）的失败或耐药性发展成为骨转移去势抵抗性前列腺癌（BmCRPC）的患者的选择仍然有限，多西他赛（DTX）是一线治疗方法之一。据报道，甾醇调节元件结合蛋白1（SREBP1）调节异常的脂质代谢，并促进前列腺癌（PCa）的进展和转移。siRNA干扰SREBP1与DTX结合可提供有效的治疗。

方法：在这项研究中，硫辛酸（LA）和交联的肽-硫辛酸胶束被交联（LC）用于DTX和siSREBP1递送（LC / D / siR）。然后，将PCa细胞（Pm）和骨髓间充质干细胞（Bm）的细胞膜融合起来，以掩盖LC / D / siR（PB @ LC / D / siR）。最后，在体外和体内对合成的PB @ LC / D / siR进行了评估。

结果：PB @ LC / D / siR通过溶酶体逃逸机制被内在PCa细胞中。使用骨转移性CRPC（BmCRPC）模型在体外和体内评估了肿瘤靶向和骨归巢研究。此外，在体外观察到DTX和siSREBP1负载的PB @ LC（PB @ LC / D / siR）的增强的抗增殖，抗迁移和抗侵袭能力。此外，PB @ LC / D / siR能够有效地抑制肿瘤的生长，并具有深层的肿瘤渗透性，高安全性和对肿瘤部位骨的良好保护。此外，PB @ LC / D / siR能够显着下调SREBP1和SCD1的mRNA和蛋白水平。

结论：本研究提出了用于骨转移性CRPC的骨癌双靶仿生纳米递送系统。