Cancer metastasis poses significant challenges in current clinical therapy. Osthole (OST) has demonstrated efficacy in treating cervical cancer and inhibiting metastasis. Despite these positive results, its limited solubility, poor oral absorption, low bioavailability, and photosensitivity hinder its clinical application. To address this limitation, a glutathione (GSH)-responded nano-herb delivery system (HA/MOS@OST&L-Arg nanoparticles, HMOA NPs) is devised for the targeted delivery of OST with cascade-activatable nitric oxide (NO) release. The HMOA NPs system is engineered utilizing enhanced permeability and retention (EPR) effects and active targeting mediated by hyaluronic acid (HA) binding to glycoprotein CD44. The cargoes, including OST and L-Arginine (L-Arg), are released rapidly due to the degradation of GSH-responsive mesoporous organic silica (MOS). Then abundant reactive oxygen species (ROS) are produced from OST in the presence of high concentrations of NAD(P)H quinone oxidoreductase 1 (NQO1), resulting in the generation of NO and subsequently highly toxic peroxynitrite (ONOO-) by catalyzing guanidine groups of L-Arg. These ROS, NO, and ONOO- molecules have a direct impact on mitochondrial function by reducing mitochondrial membrane potential and inhibiting adenosine triphosphate (ATP) production, thereby promoting increased apoptosis and inhibiting metastasis. Overall, the results indicated that HMOA NPs has great potential as a promising alternative for the clinical treatment of cervical cancer. The nano-herb delivery system (HA/MOS@OST&L-Arg nanoparticles, HMOA NPs) is successfully prepared using a combination of tumor-targeted hyaluronic acid (HA), glutathione (GSH)-responsive mesoporous organic silica (MOS), osthole (OST), and L-Arginine (L-Arg) through an assembling strategy. This tumor-specific nano-herb delivery system not only improved the bioavailability of OST but also utilized nitric oxide gas therapy to effectively suppress cervical cancer metastasis through multiple pathways and improved cancer treatment both in vitro and in vivo. image
基金:
National Key Research and Development Project of China [2023YFC3402100]; National Natural Science Foundation of China [82341004, 82130082, 82103056]; A 1<middle dot>3<middle dot>5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYGD22007]
第一作者机构:[1]Chengdu Univ Tradit Chinese Med, Sch Basic Med Sci, Chengdu 611137, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Chengdu Univ Tradit Chinese Med, Sch Basic Med Sci, Chengdu 611137, Peoples R China[2]Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China[3]Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China[4]Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China[5]Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China
推荐引用方式(GB/T 7714):
Chen Lihua,Ming Hui,Li Bowen,et al.Tumor-Specific Nano-Herb Delivery System with High L-Arginine Loading for Synergistic Chemo and Gas Therapy against Cervical Cancer[J].SMALL.2024,20(45):doi:10.1002/smll.202403869.
APA:
Chen, Lihua,Ming, Hui,Li, Bowen,Yang, Chen,Liu, Shanshan...&Yang, Zhuo.(2024).Tumor-Specific Nano-Herb Delivery System with High L-Arginine Loading for Synergistic Chemo and Gas Therapy against Cervical Cancer.SMALL,20,(45)
MLA:
Chen, Lihua,et al."Tumor-Specific Nano-Herb Delivery System with High L-Arginine Loading for Synergistic Chemo and Gas Therapy against Cervical Cancer".SMALL 20..45(2024)