5-Fluorouracil Loaded Prebiotic-Probiotic Liposomes Modulating Gut Microbiota for Improving Colorectal Cancer Chemotherapy

被引:2
作者
Sun, Xujie [1 ,2 ,3 ]
Shan, Xiaoting [2 ,3 ]
Zhu, Binyu [2 ,3 ]
Cai, Ying [2 ,3 ]
He, Zongyan [1 ]
Zhou, Lingli [2 ,3 ]
Yin, Lixuan [1 ]
Liu, Yiran [1 ]
Liu, Kaiyue [1 ]
Zhang, Tian [1 ]
Yang, Ning [1 ]
Li, Yaping [2 ,3 ]
Lang, Tianqun [1 ]
机构
[1] Lingang Lab, Shanghai 200031, Peoples R China
[2] Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
[3] Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
基金
国家重点研发计划;
关键词
5-fluorouracil; colorectal cancer; gut microbiota; prebiotics; xylan; DELIVERY; THERAPY;
D O I
10.1002/adhm.202403587
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The gut microbiota exerts inhibitory effects on the occurrence and progression of colorectal cancer (CRC) through various mechanisms. Compared to traditional microbiota regulation methods, prebiotics and probiotics demonstrate significant advantages in terms of safety and patient adaptability. Their synergy not only improves the intestinal environment but also enhances the host's anti-tumor immune response. 5-Fluorouracil (5-FU) is a first-line chemotherapy drug that has a short half-life and low bioavailability. However, if administered in an untargeted manner, 5-FU also causes adverse reactions. Liposomes can improve the pharmacokinetic profile of drugs and provide targeted delivery to the tumor site, thereby reducing side effects. In this work, a 5-FU-loaded liposome is modified with the prebiotic xylan derivative Sxy and the probiotic Akkermansia muciniphila active phospholipid homolog 1,2-dipalmitoylphosphatidy-lethanolamine (DPPE) to construct FLSK. The latter effectively prolongs the intestinal transport and release of 5-FU, maintaining high drug concentrations at the tumor site. FLSK is found to inhibit tumor growth and significantly extends the survival period of mice. In addition, FLSK promotes anti-tumor immunity and regulation of the gut microbiota. Combining the merits of prebiotics and probiotics, FLSK provides a potential strategy for integrating chemotherapy with gut microbiota regulation therapy for the treatment of CRC.
引用
收藏
页数:13
相关论文
共 41 条
[1]   Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis [J].
Ansaldo, Eduard ;
Slayden, Leianna C. ;
Ching, Krystal L. ;
Koch, Meghan A. ;
Wolf, Natalie K. ;
Plichta, Damian R. ;
Brown, Eric M. ;
Graham, Daniel B. ;
Xavier, Ramnik J. ;
Moon, James J. ;
Barton, Gregory M. .
SCIENCE, 2019, 364 (6446) :1179-+
[2]   Fecal microbiota transplantation in disease therapy [J].
Antushevich, Hanna .
CLINICA CHIMICA ACTA, 2020, 503 :90-98
[3]   Akkermansia muciniphila phospholipid induces homeostatic immune responses [J].
Bae, Munhyung ;
Cassilly, Chelsi D. ;
Liu, Xiaoxi ;
Park, Sung-Moo ;
Tusi, Betsabeh Khoramian ;
Chen, Xiangjun ;
Kwon, Jaeyoung ;
Filipcik, Pavel ;
Bolze, Andrew S. ;
Liu, Zehua ;
Vlamakis, Hera ;
Graham, Daniel B. ;
Buhrlage, Sara J. ;
Xavier, Ramnik J. ;
Clardy, Jon .
NATURE, 2022, 608 (7921) :168-+
[4]   Liposomal Drug Delivery and Its Potential Impact on Cancer Research [J].
Bhattacharya, Sankha ;
Saindane, Dnyanesh ;
Prajapati, Bhupendra G. .
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2022, 22 (15) :2671-2683
[5]   Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review [J].
Biller, Leah H. ;
Schrag, Deborah .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2021, 325 (07) :669-685
[6]   Effect of treatment with Lactococcus lactis NZ9000 on intestinal microbiota and mucosal immune responses against Clostridium perfringens in broiler chickens [J].
Boodhoo, Nitish ;
Shojadoost, Bahram ;
Alizadeh, Mohammadali ;
Astill, Jake ;
Behboudi, Shahriar ;
Sharif, Shayan .
FRONTIERS IN MICROBIOLOGY, 2023, 14
[7]   Prebiotics may reduce serum concentrations of C-reactive protein and ghrelin in overweight and obese adults: a systematic review and meta-analysis [J].
Borges, Dayanne da Silva ;
Fernandes, Ricardo ;
Mello, Arthur Thives ;
Fontoura, Ethiene da Silva ;
Soares dos Santos, Adair Roberto ;
Santos de Moraes Trindade, Erasmo Benicio .
NUTRITION REVIEWS, 2020, 78 (03) :235-248
[8]   Xylan in drug delivery: A review of its engineered structures and biomedical applications [J].
da Costa Urtiga, Silvana Cartaxo ;
Marcelino, Henrique Rodrigues ;
Tabosa do Egito, Eryvaldo Socrates ;
Oliveira, Elquio Eleamen .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2020, 151 :199-208
[9]   Intracellular Reduction-Responsive Molecular Targeted Nanomedicine for Hepatocellular Carcinoma Therapy [J].
Ding, Lei ;
Zhang, Ping ;
Huang, Xu ;
Yang, Kunmeng ;
Liu, Xingkai ;
Yu, Zhenxiang .
FRONTIERS IN PHARMACOLOGY, 2022, 12
[10]   Oral delivery of micro/nanoparticulate systems based on natural polysaccharides for intestinal diseases therapy: Challenges, advances and future perspectives [J].
dos Santos, Aline Martins ;
Carvalho, Suzana Gonsalves ;
Meneguin, Andreia Bagliotti ;
Sabio, Rafael Miguel ;
Gremiao, Maria Palmira Daflon ;
Chorilli, Marlus .
JOURNAL OF CONTROLLED RELEASE, 2021, 334 :353-366