Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, China.
Drug Deliv. 2020 Dec;27(1):1319-1328. doi: 10.1080/10717544.2020.1815897.
Cancers continue to be the second leading cause of death worldwide. Despite the development and improvement of surgery, chemotherapy and radiotherapy in cancer management, effective tumor ablation strategies are still in need due to high cancer patient mortality. Hence, we have established a new approach to achieve treatment-actuated modifications in a tumor microenvironment by using synergistic activity between two potential anticancer drugs. Dual drug delivery of Regorafenib (REGO) and Cisplatin (PT) exhibits a great anticancer potential, as REGO enhances the effect of PT treatment of human cells by providing stability of the microenvironment. However, encapsulation of REGO and PT fanatical by methoxypoly(ethylene glycol)-block-poly(D, L-lactic acid) (PEG-PLA in termed as NPs) is incompetent owing to unsuitability between the binary Free REGO and PT core and the polymeric system. Now, we display that PT can be prepared by hydrophobic coating of the dual drug centers with dioleoylphosphatidic acid (DOPA). The DOPA-covered PT can be co-encapsulated in PLGA NPs alongside REGO to stimulate excellent anticancer property. The occurrence of the PT suggestively enhanced the encapsulations of REGO into PLGA NPs (REGO-PT NPs). Further, the morphology of REGO NPs, PT NPs, and REGO-PT NPs and nanoparticle size was examined by transmission microscopy (TEM), respectively. Furthermore REGO-PT NPs induced significant apoptosis in human lung A549 and ovarian A2780 cancer cells by in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assayes (AO-EB, Nuclear Staining and Annexin V-FITC). In a xenograft model of lung cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose. Our results suggest that a hydrophobic and highly toxic drug can be rationally converted into a pharmacologically efficient and self-deliverable nursing care of nanotherapy. Highlights Dual drug delivery of Regorafenib (REGO) and Cisplatin (PT) exhibits a great anticancer potential, as REGO enhances the effect of PT treatment of human cells by providing stability of the microenvironment. REGO-PT NPs induced significant apoptosis in human lung A549 and ovarian A2780 cancer cells by in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assayes. In a xenograft model of lung cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose.
癌症仍然是全球第二大死亡原因。尽管在癌症管理中手术、化疗和放疗得到了发展和改进，但由于癌症患者死亡率高，仍需要有效的肿瘤消融策略。因此，我们建立了一种新的方法，通过两种潜在的抗癌药物的协同作用，在肿瘤微环境中实现治疗触发的修饰。雷戈非尼（REGO）和顺铂（PT）的双重药物递送显示出巨大的抗癌潜力，因为 REGO 通过提供微环境的稳定性增强了 PT 对人细胞的治疗效果。然而，由于二元游离 REGO 和 PT 核心与聚合体系之间的不兼容性，REGO 和 PT 的封装是无能的。现在，我们发现 PT 可以通过二油酰磷脂酸（DOPA）的疏水性涂层来制备。用 DOPA 覆盖的 PT 可以与 REGO 一起共包封在 PLGA NPs 中，以刺激优异的抗癌特性。PT 的出现显著增强了 REGO 进入 PLGA NPs 的包封（REGO-PT NPs）。此外，通过透射显微镜（TEM）分别检查了 REGO NPs、PT NPs 和 REGO-PT NPs 的形态和纳米颗粒大小。此外，REGO-PT NPs 在体外显著诱导人肺癌 A549 和卵巢 A2780 癌细胞凋亡。形态学观察和凋亡通过各种生化测定（AO-EB、核染色和 Annexin V-FITC）得到证实。在肺癌的异种移植模型中，这种纳米治疗在给予可耐受剂量时显示出持久的肿瘤进展抑制作用。我们的结果表明，一种疏水性和高毒性药物可以被合理地转化为一种具有药理功效和自递药的纳米治疗护理。
亮点
雷戈非尼（REGO）和顺铂（PT）的双重药物递送显示出巨大的抗癌潜力，因为 REGO 通过提供微环境的稳定性增强了 PT 对人细胞的治疗效果。
REGO-PT NPs 在体外显著诱导人肺癌 A549 和卵巢 A2780 癌细胞凋亡。
形态学观察和凋亡通过各种生化测定得到证实。
在肺癌的异种移植模型中，这种纳米治疗在给予可耐受剂量时显示出持久的肿瘤进展抑制作用。
