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Published on: February 5, 2019
"Layer peeling" co-delivery system for enhanced RNA interference-based tumor associated macrophages-specific
Tianqi Wang1, Weiwei Mu1, Feifei Li1
1Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China. zhangnancy9@sdu.edu.cn.
A novel "layer peeling" co-delivery system effectively combines RNA interference (RNAi) immunotherapy and chemotherapy. This system precisely targets tumor cells and immune cells, enhancing cancer treatment efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- RNA interference (RNAi)-based immunotherapy combined with chemotherapy shows promise for cancer treatment.
- Physiological barriers impede the transport of therapeutic agents, limiting RNAi-based chemoimmunotherapy development.
- Co-delivery systems are crucial for improving therapeutic agent co-localization and cell-specific targeting.
Purpose of the Study:
- To develop a novel multilayer co-delivery system for combined RNAi-based immunotherapy and chemotherapy.
- To achieve xenotype cell-targeting, delivering immunotherapy agents to immune cells and chemotherapy drugs to tumor cells.
- To investigate the efficacy of a "layer peeling" co-delivery system (CDMPR) for cancer treatment.
Main Methods:
- Development of a "layer peeling" co-delivery system (CDMPR) co-loading IKKβ-siRNA and doxorubicin (DOX).
- In vitro transwell assays and in vivo immunofluorescence assays in Hepa1-6 tumor-bearing mice.
- Assessment of CDMPR's pH-sensitive disassembly, cell-specific delivery, and M2-type TAM polarization capabilities.
Main Results:
- CDMPR demonstrated pH-sensitive disassembly in tumor tissue.
- IKKβ-siRNA was precisely delivered to M2-type TAMs, and DOX was internalized into tumor cells.
- CDMPR successfully polarized M2-type TAMs to M1-type TAMs both in vitro and in vivo, improving antitumor efficiency.
Conclusions:
- The developed "layer peeling" co-delivery system (CDMPR) effectively combines RNAi-based TAM polarization and chemotherapy.
- CDMPR achieves enhanced chemoimmunotherapy effects through precise delivery of therapeutic agents.
- This strategy offers a novel approach to improve cancer therapeutic outcomes.
