Acidic tumor microenvironment-sensitive liposomes enhance colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts.
Chenglei LiZhaohuan LiXue GongJianhao LiuTingyue ZhengFangqing WangJing-Liang WuBo ZhangPublished in: Nanoscale (2021)
Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the "soil" in the tumor microenvironment (TME). Accordingly, it would be a promising strategy to enhance the antitumor effect by killing both tumor cells and CAFs simultaneously. Herein, novel TME acid-responsive liposomes for co-delivery of IRI and 398 (IRI&398-s-LPs) were developed, in which the rapid release of both drugs could be triggered under acidic conditions. Notably, a CT-26/3T3 cell co-culture system was used to mimic the real TME both in vitro and in vivo. Cellular immunofluorescence revealed that IRI&398-s-LPs could efficiently decrease the activation of CAFs. In vitro cytotoxicity evaluation demonstrated that IRI&398-s-LPs exhibited higher cytotoxicity than the other liposomal formulations in the CT-26 and CT-26/3T3 cell co-culture system. In vivo NIRF imaging showed that the IRI&398-s-LPs could increase drug accumulation in the tumor sites. Furthermore, IRI&398-s-LPs not only presented superior in vivo anti-tumor activity in CT-26 bearing BALB/c mice, but also enhanced the effect in CT-26/3T3 cell bearing mice with decreased collagen and CAF biomarker expression. Furthermore, IRI&398-s-LPs also presented superior anti-metastatic efficiency in a lung metastasis model. These results indicated that this combinational strategy for eliminating both tumor cells and CAFs provides a new approach for cancer therapy, and the prepared TME-responsive liposomes for co-delivery of drugs hold promising clinical application prospects.
Keyphrases
- inflammatory response
- image quality
- cancer therapy
- dual energy
- anti inflammatory
- drug delivery
- computed tomography
- contrast enhanced
- positron emission tomography
- magnetic resonance imaging
- small cell lung cancer
- high resolution
- poor prognosis
- emergency department
- photodynamic therapy
- mesenchymal stem cells
- metabolic syndrome
- drug induced
- mass spectrometry
- fluorescence imaging
- adverse drug
- replacement therapy
- loop mediated isothermal amplification