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喜树碱多功能纳米颗粒有效地实现了乳腺癌治疗效果与肠道内稳态维持之间的平衡。

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

作者信息

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

机构信息

Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

Bioact Mater. 2024 Aug 1;41:413-426. doi: 10.1016/j.bioactmat.2024.07.032. eCollection 2024 Nov.

Abstract

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 , which may be attributed to diarrhea caused by CPT, thus leading to a reduction in microbial burden; additionally, rapidly grows and occupies niches previously occupied by other bacteria that are lost due to diarrhea. PCRHNs + Laser treatment increased the abundance of (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.

摘要

喜树碱(CPT)具有强大的抗肿瘤活性;然而,其临床应用受到严重胃肠道不良反应(GAEs)的限制。尽管与CPT衍生物相关的GAEs严重程度有所降低,但这些不良反应的发生率仍然很高。CPT多功能纳米颗粒(PCRHNs)有可能提高CPT的疗效,同时减少主要靶器官的副作用;然而,PCRHNs对CPT引起的GAEs的影响仍不确定。在这里,我们研究了PCRHNs和不同剂量CPT的治疗效果,并检查了它们对肠道屏障和肠道微生物群的影响。我们发现,PCRHNs + 激光治疗的疗效优于高剂量CPT,并且PCRHNs + 激光治疗通过帮助维持肠道屏障完整性、肠道微生物群多样性和肠道微生物群丰度也带来了更大的益处。总之,与高剂量CPT治疗相比,PCRHNs + 激光治疗可以有效平衡治疗效果和GAEs。高剂量CPT促进了病原菌的富集,这可能归因于CPT引起的腹泻,从而导致微生物负荷降低;此外, 迅速生长并占据了因腹泻而丢失的其他细菌先前占据的生态位。PCRHNs + 激光治疗增加了 (益生菌)的丰度,这可能是由于PCRHNs的光热效应。这种效应增加了过氧化氢酶活性,从而促进肿瘤内过氧化氢转化为氧气并提高体内氧气水平,这有利于兼性厌氧菌的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3521/11342206/bfe6de3e183c/ga1.jpg

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