DSAPM Lab and PCFM Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China; Medical Intelligence and Innovation Academy, South University of Science and Technology Hospital, Shenzhen 518000, China.
Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 7):127467. doi: 10.1016/j.ijbiomac.2023.127467. Epub 2023 Oct 19.
Pancreatic cancer is one of the most lethal malignancies in the world and remains one of the leading causes of cancer related death. For its treatment, a lot of investigations have dealt not only with individual chemotherapy by using polymeric carriers to deliver anticancer drugs, but also with individual gene therapy by using polymeric carriers to deliver nucleic acids such as small interfering RNA (siRNA) and plasmid DNA. However, relatively few studies have been focused on the co-delivery of gene and anticancer drug by multifunctional polymeric carriers for its synergistic therapy. In this work, a DPLL-functionalized amylose (ADP) was prepared by the click reaction between azidized amylose and propargyl focal point poly(l-lysine) dendrons, and then used to co-deliver plasmid pIRES2-EGFP-TNFα and curcumin for pancreatic cancer treatment. Due to the internal hydrophobic cavity of amylose component, ADP could load efficiently curcumin with anticancer activity and showed a sustained release behavior. Moreover, the curcumin-loaded ADP could form colloidally stable nanocomplexes with plasmid DNA in aqueous system due to the existence of cationic poly(l-lysine) dendrons and exhibited high gene transfection efficiency. The in vitro and in vivo tests confirmed the effectiveness of using ADP to co-deliver plasmid pIRES2-EGFP-TNFα and curcumin for synergistic therapy of pancreatic cancer.
胰腺癌是世界上最致命的恶性肿瘤之一，也是癌症相关死亡的主要原因之一。在治疗方面，许多研究不仅涉及使用聚合物载体输送抗癌药物的个体化疗，还涉及使用聚合物载体输送核酸（如小干扰 RNA（siRNA）和质粒 DNA）的个体基因治疗。然而，相对较少的研究集中在多功能聚合物载体上共同递送基因和抗癌药物以进行协同治疗。在这项工作中，通过叠氮化淀粉与炔丙基焦点聚（L-赖氨酸）树枝状大分子之间的点击反应制备了 DPLL 功能化的直链淀粉（ADP），然后用于共同递送质粒 pIRES2-EGFP-TNFα 和姜黄素用于胰腺癌治疗。由于直链淀粉成分的内部疏水性空腔，ADP 能够有效地负载具有抗癌活性的姜黄素，并表现出持续释放行为。此外，由于存在阳离子聚（L-赖氨酸）树枝状大分子，载有姜黄素的 ADP 能够在水相中形成胶体稳定的纳米复合物与质粒 DNA，并表现出高基因转染效率。体外和体内试验证实了使用 ADP 共同递送质粒 pIRES2-EGFP-TNFα 和姜黄素用于协同治疗胰腺癌的有效性。
