Cordycepin, a derivative of the nucleotide adenosine, has displayed several pharmacological activities including enhanced apoptosis and cancer cells inhibition. However, oral administration of cordycepin has limited practical use due to its poor bioavailability in the intestine. Herein, we developed and demonstrated a hybrid nanocarrier system in the form of biloniosome-core/chitosan-shell hybrid nanocarriers (HNCs) in order to improve the bio-characteristics of cordycepin. In this study, HNCs were prepared by using a solvent (ethanol) injection method involving cordycepin as the biloniosome core and mucoadhesive chitosan biopolymer as a coating shell. Our results showed that the cordycepin-loaded HNCs were positively charged with enhanced mucoadhesive characteristics and highly stable in gastric fluid. The increased permeability of cordycepin-loaded HNCs compared with standard cordycepin was confirmed by in vitro intestinal permeation study across the human intestinal barrier. In addition, we demonstrated that the cordycepin-loaded HNCs are able to release their components in an active form resulting in enhanced anti-cancer activity in two-dimensional (2D) cell cultures as well as in three-dimensional (3D) multi-cellular spheroids of colon cancer cells. Further, quantitative real time PCR analysis of apoptotic gene expression revealed that cordycepin HNCs can induce apoptosis in cancer cells by negatively regulating the expression of B-cell lymphoma-extra large (BCL-XL). I Overall our results showed that the hybrid nanocarrier systems represent a promising strategy for improving the bio-characteristics of cordycepin which can be considered as a potential anti-cancer agent for colorectal cancer chemotherapy.

虫草素是核苷酸腺苷的衍生物，已显示出多种药理活性，包括增强的细胞凋亡和癌细胞的抑制作用。然而，由于虫草素在肠中的生物利用度较差，因此口服其用途有限。在本文中，我们开发并证明了以纳米粒核/壳聚糖-壳杂化纳米载体（HNCs）形式存在的杂化纳米载体系统，以改善虫草素的生物特性。在这项研究中，HNC是通过使用溶剂（乙醇）注射法制备的，该方法以虫草素为双核小体核心，以粘膜粘附性壳聚糖生物聚合物为涂层外壳。我们的结果表明，装载虫草素的HNC带正电荷，具有增强的粘膜粘附特性​​，在胃液中高度稳定。体外肠道渗透研究跨越了人类肠道屏障。此外，我们证明了装载虫草素的HNC能够以活性形式释放其成分，从而在二维（2D）细胞培养以及三维（3D）多细胞培养物中增强了抗癌活性结肠癌细胞的球状体。此外，对凋亡基因表达的定量实时PCR分析表明，虫草素HNCs可通过负调控B细胞淋巴瘤超大型（BCL-XL）的表达来诱导癌细胞凋亡。总的来说，我们的结果表明，杂化纳米载体系统代表了一种改善虫草素生物特性的有前途的策略，虫草素可以被认为是结直肠癌化学疗法的潜在抗癌药。