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利用 pH 敏感仿生共递送 TRAIL/R848 脂质体重塑肿瘤微环境以对抗结直肠癌。

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

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.

出版信息

Oncol Res. 2024 Oct 16;32(11):1765-1776. doi: 10.32604/or.2024.045564. eCollection 2024.

DOI:10.32604/or.2024.045564
PMID:39449815
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11497182/
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 investigations revealed the strong anti-tumor efficacy of RTL in xenograft and orthotropic models of colorectal cancer.

CONCLUSIONS

These findings collectively highlight the therapeutic potential of R848/pTRAIL-loaded liposomes in the treatment of colorectal cancer.

摘要

背景

尽管在过去几十年中抗癌疗法的发展取得了重大进展，但结直肠癌的临床治疗仍然是一项具有挑战性的任务。本研究旨在研究针对癌症的脂质体对结直肠癌的抑制作用。

材料和方法

制备了由 3β-[N-(N'，N'-二甲氨基乙烷)甲酰胺基]胆固醇（DC-CHOL）、胆固醇（CHOL）和二油酰基磷脂酰乙醇胺（DOPE）组成的摩尔比为 1:1:0.5 的脂质体，并将其用作载体来递送至编码肿瘤坏死因子相关凋亡诱导配体（pTRAIL）基因的凋亡诱导质粒，以及 Toll 样受体（TLR7）激动剂 Rsiquimod（R848）。这样设计的原理是，pTRAIL 可以通过激活 DR4/5 受体来诱导癌细胞凋亡，而 R848 可以刺激免疫微环境。

结果

实验结果表明 R848 和 pTRAIL 包封在脂质体中的协同作用（RTL）抑制结直肠癌细胞的增殖。此外，进一步的研究揭示了 RTL 在结直肠癌异种移植和原位模型中的强大抗肿瘤功效。

结论

这些发现共同强调了 R848/pTRAIL 负载的脂质体在治疗结直肠癌中的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/45693f437df8/OncolRes-32-45564-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/2705511010c0/OncolRes-32-45564-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/698d368a26ec/OncolRes-32-45564-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/664a3df9b56c/OncolRes-32-45564-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/379b3d9b67b4/OncolRes-32-45564-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/b118e346dd89/OncolRes-32-45564-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/5b6cda594902/OncolRes-32-45564-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/45693f437df8/OncolRes-32-45564-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/2705511010c0/OncolRes-32-45564-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/698d368a26ec/OncolRes-32-45564-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/664a3df9b56c/OncolRes-32-45564-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/379b3d9b67b4/OncolRes-32-45564-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/b118e346dd89/OncolRes-32-45564-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/5b6cda594902/OncolRes-32-45564-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d84/11497182/45693f437df8/OncolRes-32-45564-f007.jpg

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