Liu Dongmei, Zhang Wenguang, Liu Xinju, Qiu Rongliang
Department of Radiation Oncology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Drug Deliv. 2021 Dec;28(1):776-786. doi: 10.1080/10717544.2021.1902022.
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 gemcitabine (GEM) and cisplatin (PT) exhibits a great anticancer potential, as GEM enhances the effect of PT treatment of human cells by providing stability of the microenvironment. However, encapsulation of GEM 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 GEM and PT core and the macromolecular 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 GEM to stimulate excellent anticancer property. The occurrence of the PT suggestively enhanced the encapsulations of GEM into PLGA NPs (GEM-PT NPs). Further, the morphology of GEM NPs, PT NPs, and GEM-PT NPs and nanoparticle size was examined by transmission microscopy (TEM), respectively. Furthermore GEM-PT NPs induced significant apoptosis in human nasopharyngeal carcinoma CNE2 and SUNE1 cancer cells by . The morphological observation and apoptosis were confirmed by the various biochemical assays (AO-EB, nuclear staining, and annexin V-FITC). In a xenograft model of nasopharyngeal cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose. Our results suggest that a macromolecular hydrophobic and highly toxic drug can be rationally converted into a pharmacologically efficient and self-deliverable of nanotherapy.
癌症仍然是全球第二大死因。尽管在癌症治疗中手术、化疗和放疗有了发展和改进，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，我们建立了一种新方法，通过利用两种潜在抗癌药物之间的协同活性，在肿瘤微环境中实现治疗驱动的修饰。吉西他滨（GEM）和顺铂（PT）的双药递送显示出巨大的抗癌潜力，因为GEM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，由于游离的GEM和PT核心与大分子系统之间不匹配，用甲氧基聚（乙二醇）-嵌段-聚（D，L-乳酸）（称为NPs的PEG-PLA）对GEM和PT进行狂热封装是无效的。现在，我们展示了可以通过用二油酰磷脂酸（DOPA）对双药中心进行疏水包覆来制备PT。DOPA包覆的PT可以与GEM一起共封装在PLGA NPs中，以激发优异的抗癌性能。PT的存在显著增强了GEM在PLGA NPs（GEM-PT NPs）中的封装。此外，分别通过透射显微镜（TEM）检查了GEM NPs、PT NPs和GEM-PT NPs的形态以及纳米颗粒大小。此外，GEM-PT NPs通过……在人鼻咽癌CNE2和SUNE1癌细胞中诱导了显著的细胞凋亡。通过各种生化分析（AO-EB、核染色和膜联蛋白V-FITC）证实了形态观察和细胞凋亡。在鼻咽癌异种移植模型中，这种纳米疗法在给予可耐受剂量后显示出对肿瘤进展的持久抑制。我们的结果表明，一种大分子疏水且剧毒的药物可以合理地转化为一种药理学上高效且可自我递送的纳米疗法。
