Remodeling tumor microenvironment using pH-sensitive biomimetic co-delivery of TRAIL/R848 liposomes against colorectal cancer
YONGJIAN HUANG, JINZHOU WANG, JIUHUA XU, NING RUAN*
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China
* Corresponding Author: NING RUAN. Email: 
Oncology Research https://doi.org/10.32604/or.2024.045564
Received 31 August 2023; Accepted 11 January 2024; Published online 04 June 2024
Abstract
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.
Graphical Abstract
Keywords
Colorectal cancer; Plasmid TRAIL (pTRAIL); R848; Tumor-associated macrophages
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