Remodeling tumor microenvironment using pH-sensitive biomimetic co-delivery of TRAIL/R848 liposomes against colorectal cancer  

作　　者：YONGJIAN HUANG JINZHOU WANG JIUHUA XU NING RUAN 

机构地区：[1]Department of Gastrointestinal Surgery,The First Affiliated Hospital of Fujian Medical University,Fuzhou,350005,China

出　　处：《Oncology Research》2024年第11期1765-1776,共12页肿瘤学研究（英文）

基　　金：approved by the Institutional Animal Care and Use Committee(IACUC)of the First Affiliated Hospital of Fujian Medical University(No.2023048).

摘　　要：Background:Despite significant advancements in the development of anticancer therapies over the past few decades,the clinical management of colorectal cancer remains a challenging task.This study aims to investigate the inhibitory effects of cancer-targeting liposomes against colorectal cancer.Materials and Methods:Liposomes consisting of 3β-[N-(N′,N′-dimethylamino ethane)carbamoyl]-cholesterol(DC-CHOL),cholesterol(CHOL),and dioleoylphosphatidylethanolamine(DOPE)at a molar ratio of 1:1:0.5 were created and used as carriers to deliver an apoptosis-inducing plasmid encoding the tumor necrosis factor-related apoptosis-inducing ligand(pTRAIL)gene,along with the toll-like receptor(TLR7)agonist Rsiquimod(R848).The rationale behind this design is that pTRAIL can trigger cancer cell apoptosis by activating the DR4/5 receptor,while R848 can stimulate the immune microenvironment.Results:Experimental results demonstrated the synergistic effects of R848 and pTRAIL encapsulated by liposomes(RTL)in suppressing the proliferation of colorectal cancer cells.Moreover,further in vivo investigations revealed the strong anti-tumor efficacy of RTL in xenograft and orthotropic in situ models of colorectal cancer.Conclusions:These findings collectively highlight the therapeutic potential of R848/pTRAIL-loaded liposomes in the treatment of colorectal cancer.

关 键 词：Colorectal cancer Plasmid TRAIL(pTRAIL) R848 Tumor-associated macrophages 

分 类 号：R730.2[医药卫生—肿瘤]