Ding Qiongjie, Xu Zhijue, Zhou Luyi, Rao Congying, Li Weimin, Muddassir Mohd, Sakiyama Hiroshi, Li Bo, Ouyang Qin, Liu Jianqiang
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China; Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan 523808, China.
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
J Colloid Interface Sci. 2022 Sep;621:180-194. doi: 10.1016/j.jcis.2022.04.078. Epub 2022 Apr 15.
Chemodynamic therapy when combined with chemotherapy opens up a new avenue for treatment of cancer. However, its development is still restricted by low targeting, high dose and toxic side effects. Herein, rational designing and construction of a new multifunctional platform with the core-shell structure 5-ALA@UiO-66-NH-FAM@CP1 (ALA = 5-aminolevulinic acid, CP1 = zirconium-pemetrexed (Zr-MTA)) has been performed. In this platform, CP1 acting as a shell is encapsulated with the UiO-66-NH to engender a core-shell structure that promotes and achieves a high MTA loading rate through high affinity between MTA and unsaturated Zr site of UiO-66-NH. The 5-ALA and 5-carboxyl fluorescein (5-FAM) was successfully loaded and covalently combined with UiO-66-NH due to its high porosity and presence of amino groups. The characterization results indicated that the loading rate of MTA (41.03 wt%) of platform is higher than the reported values. More importantly, the in vitro and in vivo results also demonstrated that it has a good folate targeting ability and realizes high efficient antitumor activity by chemotherapy combied with photodynamic therapy (PDT). This newly developed multifunctional platform could provide a new idea for designing and constructing the carrier with chemotherapy and PDT therapy.
化学动力疗法与化疗联合使用为癌症治疗开辟了一条新途径。然而,其发展仍受到低靶向性、高剂量和毒副作用的限制。在此,已进行了具有核壳结构5-氨基乙酰丙酸@UiO-66-NH-荧光素@CP1(ALA = 5-氨基乙酰丙酸,CP1 = 锆-培美曲塞(Zr-MTA))的新型多功能平台的合理设计与构建。在该平台中,作为壳层的CP1被UiO-66-NH包裹,形成核壳结构,通过MTA与UiO-66-NH的不饱和Zr位点之间的高亲和力促进并实现了高MTA负载率。5-ALA和5-羧基荧光素(5-FAM)因其高孔隙率和氨基的存在而成功负载并与UiO-66-NH共价结合。表征结果表明该平台的MTA负载率(41.03 wt%)高于报道值。更重要的是,体外和体内结果还表明它具有良好的叶酸靶向能力,并通过化疗与光动力疗法(PDT)联合实现了高效抗肿瘤活性。这种新开发的多功能平台可为设计和构建具有化疗和PDT治疗功能的载体提供新思路。