Kaveh Zenjanab Masoumeh, Abdolahinia Elaheh Dalir, Alizadeh Effat, Hamishehkar Hamed, Shahbazi Rasoul, Ranjbar-Navazi Zahra, Jahanban-Esfahlan Rana, Fathi Marziyeh, Mohammadi Seyed Abolghasem
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 51656-65931, Iran.
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz 51656-65931, Iran.
ACS Omega. 2024 Feb 22;9(9):10875-10885. doi: 10.1021/acsomega.3c09782. eCollection 2024 Mar 5.
Chemotherapy is widely used for cancer therapy; however, its efficacy is limited due to poor targeting specificity and severe side effects. Currently, the next generations of delivery systems with multitasking potential have attracted significant attention for cancer therapy. This study reports on the design and synthesis of a multifunctional nanoplatform based on niosomes (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug commonly used to treat breast cancer, and sodium oxamate (SO), a glycolytic inhibitor to enhance the cytotoxicity of anticancer drug, along with quantum dots (QD) as bioimaging agents, and hyaluronic acid (HA) coating for active targeting. HN@QPS nanoparticles with a size of ∼150 nm and a surface charge of -39.9 mV with more than 90% EE for PTX were synthesized. Codelivery of SO with PTX remarkably boosted the anticancer effects of PTX, achieving IC values of 1-5 and >0.5 ppm for HN@QP and HN@QPS, respectively. Further, HN@QPS treatment enhanced the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on HHF-2 normal cells. Also, quantification of mitochondrial fluorescence showed efficient toxicity against MCF-7 cells. Moreover, the cellular uptake evaluation demonstrated an improved uptake of HN@Q in MCF-7 cells. Taken together, this preliminary research indicated the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic against breast cancer cells.
化疗被广泛用于癌症治疗；然而，由于靶向特异性差和严重的副作用，其疗效有限。目前，具有多任务潜力的下一代递送系统在癌症治疗方面引起了广泛关注。本研究报道了一种基于脂质体（NIO）的多功能纳米平台的设计与合成，该脂质体共负载了紫杉醇（PTX，一种常用于治疗乳腺癌的化疗药物）和草酸钠（SO，一种糖酵解抑制剂以增强抗癌药物的细胞毒性），同时还负载了作为生物成像剂的量子点（QD）以及用于主动靶向的透明质酸（HA）涂层。合成了尺寸约为150 nm、表面电荷为 -39.9 mV且紫杉醇包封率超过90%的HN@QPS纳米颗粒。SO与PTX的共递送显著增强了PTX的抗癌效果，HN@QP和HN@QPS的IC值分别达到1 - 5 ppm和>0.5 ppm。此外，HN@QPS处理使MCF - 7乳腺癌细胞的凋亡率提高了70%以上，而对HHF - 2正常细胞无明显细胞毒性。同时，线粒体荧光定量显示对MCF - 7细胞具有高效毒性。此外，细胞摄取评估表明MCF - 7细胞对HN@Q的摄取有所改善。综上所述，这项初步研究表明HN@QPS作为一种针对乳腺癌细胞的高效靶向双药递送纳米诊疗剂具有潜力。
