Medhi Himadri, Khumukcham Saratchandra Singh, Manavathi Bramanandam, Paik Pradip
School of Engineering Sciences and Technology, University of Hyderabad Hyderabad 500046 India.
Department of Biochemistry, School of Life Sciences, University of Hyderabad Hyderabad 500046 India
RSC Adv. 2020 Jun 24;10(40):24095-24107. doi: 10.1039/d0ra04505e. eCollection 2020 Jun 19.
Among the breast cancers, triple negative breast cancer (TNBC) has relatively poor outcomes with a lower survival rate and personalised chemotherapy is the only option available for treatment. Currently in the biomedical domain, nanomaterials with porous morphology have revealed their tremendous possibilities to be used as a nanocarrier in treating cancer by offering void space to encapsulate/entrap biological agents. However, the development of nanocarrier-based targeted therapy with high therapeutic efficacy and fewer side effects to normal cells is always a challenge. Here, we have developed nanocargos based on biodegradable mesoporous PCL (polycaprolactone) of approx. diameter of 75 nm by template removal synthesis techniques. Succeeding the comparative analysis of the nanocarriers, the efficiencies of core shell PCL-mZnO (PZ) and mesoporous PCL (HPZ) to deliver paclitaxel (Taxol/T) into breast cancer cells, is investigated. We found that HPZ nanocapsules have less cytotoxicity and drug loading efficiency of about 600 μg mg. The Taxol-loaded nanoparticles (T-HPZ) have exhibited more cytotoxicity than Taxol alone treated cancer cells. Furthermore, T-HPZ treated MDA-MB231 cells are accumulated at G2/M phase of the cell cycle and eventually undergo apoptosis. In support of this, anchorage independent growth of MDA-MB231 cells are significantly inhibited by T-HPZ treatment. Together, our findings suggest that T-HPZ-based paclitaxel (Taxol/T) loaded nanoparticles provide a novel therapeutic option in the treatment of TNBC.
在乳腺癌中,三阴性乳腺癌(TNBC)的预后相对较差,生存率较低,个性化化疗是唯一可用的治疗选择。目前在生物医学领域,具有多孔形态的纳米材料已显示出巨大的潜力,可通过提供空隙空间来封装/包裹生物制剂,用作癌症治疗的纳米载体。然而,开发具有高治疗效果且对正常细胞副作用较小的基于纳米载体的靶向治疗一直是一项挑战。在此,我们通过去除模板合成技术,开发了基于直径约75nm的可生物降解介孔聚己内酯(PCL)的纳米载体。在对纳米载体进行比较分析之后,研究了核壳PCL-mZnO(PZ)和介孔PCL(HPZ)将紫杉醇(Taxol/T)递送至乳腺癌细胞的效率。我们发现HPZ纳米胶囊的细胞毒性较小,药物负载效率约为600μg/mg。负载紫杉醇的纳米颗粒(T-HPZ)比单独用紫杉醇处理的癌细胞表现出更高的细胞毒性。此外,T-HPZ处理的MDA-MB231细胞在细胞周期的G2/M期积累,并最终发生凋亡。支持这一观点的是,T-HPZ处理可显著抑制MDA-MB231细胞的非贴壁依赖性生长。总之,我们的研究结果表明,基于T-HPZ的负载紫杉醇(Taxol/T)的纳米颗粒为三阴性乳腺癌的治疗提供了一种新的治疗选择。