1.Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor
Min MU ; Xiaoyan LIANG ; Na ZHAO ; Di CHUAN ; Bo CHEN ; Shasha ZHAO ; Guoqing WANG ; Rangrang FAN ; Bingwen ZOU ; Bo HAN ; Gang GUO
Journal of Pharmaceutical Analysis 2023;13(1):99-109
Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.
2.Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy
Fan RANGRANG ; Cai LINRUI ; Liu HAO ; Chen HONGXU ; Chen CAILI ; Guo GANG ; Xu JIANGUO
Journal of Pharmaceutical Analysis 2024;14(3):321-334
Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met-GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met-GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nano-platform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
3. Effect of recipient SLCO1B1 rs2291075 polymorphism on tacrolimus dose-corrected trough concentration in early postoperative period of liver transplantation
Yi WU ; Rangrang WANG ; Zhaowen WANG ; Junwei FAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2020;25(11):1268-1275
AIM: To explore the relationship between SLCO1B1 rs2291075 polymorphism and tacrolimus (FK506) dose-corrected trough concentration (C/D, ng•mL