Camptothecin multifunctional nanoparticles effectively achieve a balance between the efficacy of breast cancer treatment and the preservation of intestinal homeostasis  

作　　者：Qingya Liu Yun Yang Meng Pan Kun Shi Dong Mo Yicong Li Meng Wang Linfeng Guo Zhiyong Qian 

机构地区：[1]Department of Biotherapy,Cancer Center and State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu,610041,China [2]Department of Plastic and Burn Surgery,West China Hospital,Sichuan University,Chengdu,610041,China

出　　处：《Bioactive Materials》2024年第11期413-426,共14页生物活性材料（英文）

基　　金：National Natural Science Foundation of China Regional Innovation and Development Joint Fund(NSFCU21A20417);National Natural Science Foundation of China(NSFC31930067,NSFC32001003,NSFC82202320);Natural Science Foundation of Sichuan Province(2022NSFSC1282);135 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD18002);We also thank the support by Post-Doctor Research Project,West China Hospital,Sichuan University(2023HXBH011,19HXBH099);Postdoctoral Interdisciplinary Innovation Foundation Project of Sichuan University(1082204112G23);China Postdoctoral Science Foundation(2023M742476);Natural Science Foundation of Sichuan Province(2023NSFSC1585).

摘　　要：Camptothecin(CPT)exhibits potent antitumor activity;however,its clinical application is limited by significant gastrointestinal adverse effects(GAEs).Although the severity of GAEs associated with CPT derivatives has decreased,the incidence rate of these adverse effects has remained high.CPT multifunctional nanoparticles(PCRHNs)have the potential to increase the efficacy of CPT while reducing side effects in major target organs;however,the impact of PCRHNs on the GAEs from CPT remains uncertain.Here,we investigated the therapeutic effects of PCRHNs and different doses of CPT and examined their impacts on the intestinal barrier and the intestinal microbiota.We found that the therapeutic efficacy of PCRHNs+Laser treatment was superior to that of high-dose CPT,and PCRHNs+Laser treatment also provided greater benefits by helping maintain intestinal barrier integrity,intestinal microbiota diversity,and intestinal microbiota abundance.In summary,compared to high-dose CPT treatment,PCRHNs+Laser treatment can effectively balance therapeutic effects and GAEs.A high dose of CPT promotes the enrichment of the pathogenic bacteria Escherichia-Shigella,which may be attributed to diarrhea caused by CPT,thus leading to a reduction in microbial burden;additionally,Escherichia-Shigella rapidly grows and occupies niches previously occupied by other bacteria that are lost due to diarrhea.PCRHNs+Laser treatment increased the abundance of Lactobacillus(probiotics),possibly due to the photothermal effect of the PCRHNs.This effect increased catalase activity,thus facilitating the conversion of hydrogen peroxide into oxygen within tumors and increasing oxygen levels in the body,which is conducive to the growth of facultative anaerobic bacteria.

关 键 词：CAMPTOTHECIN PCRHNs Intestinal barrier Intestinal microbiota PROBIOTICS 

分 类 号：R730.5[医药卫生—肿瘤]