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Updated: Nov 2, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
Tumor progress intercept by intervening in Caveolin-1 related intercellular communication via ROS-sensitive c-Myc
Xueqing Zhou1, Xuan Liu1, Xiqin Yang1
1College of Pharmaceutical Science, Zhejiang University, Hangzhou, 310058, China.
Abstract:
Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) play an important role in the development of tumors by secreting a variety of cytokines or directly communicating with tumor cells, making TAMs-targeted therapeutic strategies very attractive. It has been reported that oncogene c-Myc is related to every aspect of the oncogenic process of tumor cells and the alternative activation of macrophages. Hence, we constructed a glycolipid nanocarrier containing ROS-responsive peroxalate linkages (CSOPOSA) for ROS-triggered release of drugs and further modified it with Ex 26 (Ex 26-CSOPOSA), a selective sphingosine 1-phosphate receptor 1 (S1PR1) antagonist, to achieve the dual-targeted delivery of the c-Myc inhibitor JQ1 via S1PR1, which is overexpressed on both tumor cells and TAMs, thereby inducing apoptosis of tumor cells, and blocking M2 polarization of macrophages. More strikingly, our studies found that JQ1 could effectively inhibit the migration of tumor cells induced by M2 macrophages-derived exosomes via blocking Caveolin-1 related intercellular exosome exchange through lncRNA H19 and miR-107. The in vivo results revealed that this dual-targeted delivery strategy effectively inhibited tumor growth and metastasis with less systemic toxicity, providing a potential method for effective tumor treatment.
Insights
This study developed a dual-targeted nanocarrier delivering a c-Myc inhibitor (JQ1) to tumor cells and macrophages. This strategy effectively inhibited tumor growth and metastasis with reduced toxicity.
Area of Science:
- Oncology
- Nanomedicine
- Immunology
Background:
- Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) significantly influence tumor progression through cytokine secretion and direct cell communication.
- Targeting TAMs presents an attractive therapeutic strategy for cancer treatment.
- The oncogene c-Myc is implicated in various aspects of tumor cell oncogenesis and macrophage activation.
Purpose of the Study:
- To develop a dual-targeted delivery system for the c-Myc inhibitor JQ1, targeting both tumor cells and TAMs.
- To investigate the therapeutic potential of this system in inhibiting tumor growth, metastasis, and M2 macrophage polarization.
- To explore the mechanism by which JQ1 inhibits tumor cell migration mediated by M2 macrophage-derived exosomes.
Main Methods:
- Construction of a glycolipid nanocarrier (CSOPOSA) with ROS-responsive peroxalate linkages for drug release.
- Modification of the nanocarrier with Ex 26, a selective sphingosine 1-phosphate receptor 1 (S1PR1) antagonist (Ex 26-CSOPOSA), for dual targeting.
- Delivery of the c-Myc inhibitor JQ1 via S1PR1, which is overexpressed on tumor cells and TAMs.
- Assessment of JQ1's effect on tumor cell apoptosis, M2 macrophage polarization, and tumor cell migration induced by exosomes.
- Investigation of the role of Caveolin-1, lncRNA H19, and miR-107 in exosome-mediated intercellular communication.
Main Results:
- The Ex 26-CSOPOSA nanocarrier successfully achieved dual-targeted delivery of JQ1.
- JQ1 induced tumor cell apoptosis and inhibited M2 polarization of macrophages.
- JQ1 effectively suppressed tumor cell migration induced by M2 macrophage-derived exosomes by disrupting exosome exchange via lncRNA H19 and miR-107.
- In vivo studies demonstrated significant inhibition of tumor growth and metastasis with reduced systemic toxicity.
Conclusions:
- The developed dual-targeted delivery strategy using Ex 26-CSOPOSA nanocarriers shows significant potential for effective cancer treatment.
- This approach offers a promising method for simultaneously targeting tumor cells and TAMs, leading to enhanced therapeutic outcomes.
- The findings highlight the intricate role of exosome communication in tumor metastasis and provide a novel therapeutic avenue targeting this pathway.
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